Joel Clinton Glover

• Ievglevskyi, Oleksandr; Zosen, Denis; Osete, Jordi Requena; Glover, Joel Clinton; Paulsen, Ragnhild Elisabeth Heimtun & Djurovic, Srdjan [Vis alle 7 forfattere av denne artikkelen] (2026). Human iPSC-Derived Spinal Cord Organoids – The First Electrophysiological Assessment of Neuronal Maturation. ACS Chemical Neuroscience. 17(16), s. 3048–3057. doi: 10.1021/acschemneuro.5c00823. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The spinal cord exhibits a complex cytoarchitecture and neuronal circuitry organization that challenges in vitro replication of its functional integrity. Here we employed a previously published protocol to generate spinal cord organoids (SCOs) from human-induced pluripotent stem cells (hiPSCs). We characterized phenotypic changes in functional neuronal properties in SCO neurons at early developmental stages (15–32 days in culture) using a quantitative electrophysiological approach. Using the whole-cell patch-clamp technique to evaluate electrophysiological properties, we found that SCO neurons exhibited progressive maturation, as evidenced by hyperpolarized resting membrane potentials, increased inward current amplitude, refined action potential kinetics, and the early emergence of mature-type firing patterns. In particular, we show that the spike frequency adaptation phenomenon, which prevails in motor neurons, appears at early stages of SCO neuron development. Immunohistochemical assessment confirmed the expression of key transcription factors in motor neurons (ISLET1 and HB9) and immature spinal interneurons (LHX1/5 and PAX2). Collectively, our findings demonstrate that neurons in hiPSC-derived SCOs exhibit physiological differentiation, which is important for using SCOs to investigate human spinal cord development and advance translational research in CNS disorders and cell replacement therapies.

• Han, Yilin; King, Marianne; Fjerdingstad, Hege Brincker; Gullo, Maurizio; Zeger, Lukas & Kádár, Roland [Vis alle 11 forfattere av denne artikkelen] (2025). Differentiation of iPSC-derived neural progenitors into motor neurons in 3D-printed bioscaffolds. International Journal of Bioprinting. ISSN 2424-7723. 11(3), s. 498–515. doi: 10.36922/ijb.5973. Fulltekst i vitenarkiv Vis sammendrag

  Translational medicine for neurodegenerative diseases can advance through the use of in vitro models incorporating human neural cells derived from patient-specific induced pluripotent stem cells (iPSCs). Previously, we investigated whether motor neuron (MN) progenitors derived from human iPSCs could differentiate from MNs within three-dimensional (3D)-printed scaffolds. While extensive neurite arborization was observed on the scaffold surface, no neurite outgrowth occurred within the scaffold interior. Here we showed the extensive growth of the neurites from iPSC-derived neural progenitors, imbedded into the gelatin scaffolds during 30 days of experimental time. We presented a bioink formulation that softens the scaffold while preserving its 3D structure, thereby facilitating neurite outgrowth throughout the scaffold. MN differentiation, evidenced by extensive neurite arborization and the expression of choline acetyltransferase (ChAT), was verified in 3D images deep within the scaffold structure. Notably, the degree of MN differentiation appeared to depend on two factors as follows: the delivery of MN differentiation factors via mesoporous silica particles (MSPs) embedded in the bioink and the method used to generate MN progenitors prior to 3D printing. In this paper, we provide a detailed protocol for 3D-printing human iPSC-derived MN progenitors, enabling their differentiation and survival within gelatin scaffolds. This protocol could be expanded to incorporate additional cell types, allowing the creation of more complex and standardized 3D neural tissues. Such advancements could facilitate investigations into the pathophysiology of motor neuron diseases and the development of new therapeutic strategies.

• Mochida, Hiraku & Glover, Joel Clinton (2025). The development of functional glutamatergic and GABAergic synaptic connections between vestibulo-ocular projection neurons and oculomotor motoneurons in the chicken embryo. Frontiers in Neurology. 16. doi: 10.3389/fneur.2025.1568926. Fulltekst i vitenarkiv Vis sammendrag

  Introduction and methods: We assessed the functional development of synapses from defined vestibulo-ocular projection neurons to motoneurons (MNs) in the oculomotor nuclear complex in the chicken embryo using optical recording of postsynaptic responses with the calcium-sensitive probe Calcium Green Dextran Amine (CGDA). The vestibulo-ocular projection neuron groups were defined according to the hodological nomenclature established by Díaz et al. (1) and encompassed the ipsilateral rostral, ipsilateral caudal and contralateral caudal vestibulo-ocular (iR-VO, iC-VO and cC-VO) groups. These groups provide differential input to the inferior rectus (IR), superior oblique (SO), superior rectus (SR) and inferior oblique IO) MN pools. The cC-VO group includes abducens interneurons (abd INs) which innervate the medial rectus (MR) MN pool. Since the SO MN pool, which projects out the trochlear nerve, was not labeled, recordings were limited to the IR, SR, IO and MR MN pools. Results: Single pulse stimulation of all the presynaptic axons collectively in wholemount preparations of the brain stem elicited robust calcium responses in all four of the CGDA-labeled postsynaptic MN pools. Responses were recorded from the dorsal surface in different regions of interest (ROIs) deployed along the mediolateral axis, which allowed us to distinguish responses in IR, MR+IO and SR MNs. Responses were first detected in a fraction of preparations at d7 of development, and from d8 in all preparations. Response magnitudes increased through d9, and then diminished through d11. Pharmacological experiments showed that responses included both glutamatergic (AMPA receptor and NMDA receptor-mediated) and GABAergic (GABAA receptor-mediated) components. All three components were present when the first responses appeared, but their proportional contribution changed during development. Covert NMDA-sensitive responses could be revealed by superfusing unresponsive d7 preparations with Mg2+-free Ringer, indicating that the very first responses to develop were mediated by NMDA receptors. GABAergic responses involved the activation of voltage-gated calcium channels and were therefore likely to be depolarizing, but nevertheless had an inhibitory effect on glutamatergic responses. Paired pulse and train stimulation at d9-d11 demonstrated substantial facilitation of the aggregate response. Discussion: These data provide new information about the functional development of vestibulo-ocular reflex (VOR) circuitry and set the stage for testing the role of specific receptors and downstream signaling in establishing the specific synaptic connections that characterize the VOR.

• Henden, Camilla; Fjerdingstad, Hege Brincker; Bjørnsen, Elisabeth Gyllensten; Thiruchelvam-Kyle, Lavanya; Daws, Michael Rory & Inngjerdingen, Marit [Vis alle 8 forfattere av denne artikkelen] (2025). NK-cell cytotoxicity toward pluripotent stem cells and their neural progeny: impacts of activating and inhibitory receptors and KIR/HLA mismatch. Stem Cells. ISSN 1066-5099. 43(3). doi: 10.1093/stmcls/sxae083. Fulltekst i vitenarkiv Vis sammendrag

  Pluripotent stem cells provide opportunities for treating injuries and previously incurable diseases. A major concern is the immunogenicity of stem cells and their progeny. Here, we have dissected the molecular mechanisms that allow natural killer (NK) cells to respond to human pluripotent stem cells, investigating a wide selection of activating and inhibitory NK-cell receptors and their ligands. Reporter cells expressing the activating receptor NKG2D responded strongly to embryonic stem (ES) cell lines and induced pluripotent stem (iPS) cell lines, whereas reporter cells expressing the activating receptors NKp30, NKp46, KIR2DS1, KIR2DS2, and KIR2DS4 did not respond. Human ES and iPS cells invariably expressed several ligands for NKG2D. Expression of HLA-C and HLA-E was lacking or low, insufficient to trigger reporter cells expressing the inhibitory receptors KIR2DL1, -2DL2, or -2DL3. Similar results were obtained for the pluripotent embryonic carcinoma cell lines NTERA-2 and 2102Ep, and also iPS-cell-derived neural progenitor cells. Importantly, neural progenitor cells and iPS-cell-derived motoneurons also expressed B7H6, the ligand for the activating receptor NKp30. In line with these observations, IL-2-stimulated NK cells showed robust cytotoxic responses to ES and iPS cells as well as to iPS-cell-derived motoneurons. No significant differences in cytotoxicity levels were observed between KIR/HLA matched and mismatched combinations of NK cells and pluripotent targets. Together, these data indicate that pluripotent stem cells and their neural progeny are targets for NK-cell killing both by failing to sufficiently express ligands for inhibitory receptors and by expression of ligands for activating receptors.

• Pabst, Oliver; Schülke, Christin; Balasingham, Ilangko; Krauss, Stefan Johannes Karl; Glover, Joel Clinton & Martinsen, Ørjan Grøttem (2025). Recording and modeling of pinched hysteresis loops, the fingerprint of a memristor, in neurons. Scientific Reports. 15. doi: 10.1038/s41598-025-21035-0. Fulltekst i vitenarkiv Vis sammendrag

  A variant of the Hodgkin-Huxley model has been proposed in which time-varying Na+ and K+ ion conductances are replaced by memristors, based on the proposal that ion channels are memristors. This hypothesis predicts that current-voltage plots of neurons subjected to sinusoidal stimulation should exhibit a pinched hysteresis loop, the fingerprint of a memristor. We tested this using whole-cell patch clamp recordings from human neurons derived from neural progenitor cells and observed pinched hysteresis loops in 16% of all recorded neurons. Recordings with current clamp and voltage clamp with a holding potential of 0 mV yielded a higher success rate than voltage clamp recordings with a holding potential of around − 60 mV. In addition, more neurons exhibited pinched hysteresis loops when the applied voltage or current amplitude was high, and the frequency was low. The recording of pinched hysteresis loops in neurons gives evidence that these contain memristors and this is the first time to be shown experimentally. This is not just an indication that the memristor-based Hodgkin-Huxley model is valid; it also demonstrates that models of neurons based on memristors actually resemble nature. We then subjected simulated neurons expressing Hodgkin-Huxley voltage-gated Na+ and K+ channels to sinusoidal membrane potential oscillations and found that the presence of pinched hysteresis loops depended strongly on the density of voltage-gated K+ channels and on the membrane capacitance but not on the presence of voltage-gated Na+ channels. Because Na+ channels are expected to be largely inactivated in neurons at a holding potential of 0 mV, these findings together suggest that it is the presence of voltage-gated K+ channels that is critical for the observed memristive behavior.

• Glover, Joel Clinton (2025). Hodological patterning as an organizing principle in vertebrate motor circuitry. Frontiers in Neuroanatomy. 18. doi: 10.3389/fnana.2024.1510944. Fulltekst i vitenarkiv Vis sammendrag

  Hodological patterning refers to developmental mechanisms that link the location of neurons in the brain or spinal cord to specific axonal trajectories that direct connectivity to synaptic targets either within the central nervous system or in the periphery. In vertebrate motor circuits, hodological patterning has been demonstrated at different levels, from the final motor output of somatic and preganglionic autonomic neurons targeting peripheral motoneurons and ganglion cells, to premotor inputs from spinal and brainstem neuron populations targeting the somatic motoneurons and preganglionic autonomic neurons, to cortical neurons that delegate movement commands to the brainstem and spinal neurons. In many cases molecular profiling reveals potential underlying mechanisms whereby selective gene expression creates the link between location and axon trajectory. At the cortical level, somatotopic organization suggests a potential underlying hodological patterning, but this has not been proven. This review describes examples of hodological patterning in motor circuits and covers current knowledge about how this patterning arises.

• Glover, Joel Clinton; Tolstenkov, Oleg & Mikhaleva, Yana (2024). Calcium signaling in tunicate development. Frontiers in Ecology and Evolution. 12. doi: 10.3389/fevo.2024.1470671. Fulltekst i vitenarkiv Vis sammendrag

  A comparative overview is provided of Ca2+ signaling and its potential mechanistic roles during development in tunicates. As background, the review presents an introduction to tunicate taxonomy, and then a general overview of Ca2+ signaling and methods for recording and measuring Ca2+ signals. It then covers the dynamics and implicated mechanisms of Ca2+ signals during different phases of development from oocyte to larva. These include signals arising in the unfertilized oocyte, signals associated with fertilization and meiosis, intercellular signals occurring from early cleavage stages through gastrulation, intercellular signals during organogenesis, and signals associated with early behavior. Comparisons are made among different tunicate species and where relevant to other chordate species. In many tunicate species, Ca2+ currents across the oocyte membrane are present prior to fertilization, and in the appendicularian Oikopleura dioica regular Ca2+ transients have been recorded optically prior to fertilization. Ca2+ signals at this stage have been implicated in pre-fertilization oocyte maturation events. The fertilization transient is the most well-studied Ca2+ signal and is triggered by factors from the sperm, including pivotally a phospholipase C (PLC) isoform that catalyzes the generation of IP3, which elicits release of Ca2+ from the endoplasmic reticulum. Post-fertilization signals are similarly dependent on IP3 signaling and are regulated by cyclin-dependent kinase 1 (Cdk1), and thereby linked to the meiotic divisions required for zygote formation. Ca2+ signals associated with early cleavages through gastrulation arise in blastomeres of the muscle lineage and spread from these in a coordinated fashion to other blastomeres through gap junctions. Post-gastrulation Ca2+ signals begin to show tissue-specificity in their temporal pattern as organogenesis proceeds, likely associated with loss of general gap junction transmission. Once neurulation has occurred, Ca2+ signals arise first in the nervous system and are transmitted synaptically to muscle, while Ca2+ signals arising spontaneously in the epidermis follow a separate temporal pattern. Species differences in the spatiotemporal characteristics of pre- and postgastrulation Ca+2 signals are discussed.

• Fritzsch, Bernd & Glover, Joel Clinton (2024). Gene networks and the evolution of olfactory organs, eyes, hair cells and motoneurons: a view encompassing lancelets, tunicates and vertebrates. Frontiers in Cell and Developmental Biology. 12. doi: 10.3389/fcell.2024.1340157. Fulltekst i vitenarkiv Vis sammendrag

  Key developmental pathways and gene networks underlie the formation of sensory cell types and structures involved in chemosensation, vision and mechanosensation, and of the efferents these sensory inputs can activate. We describe similarities and differences in these pathways and gene networks in selected species of the three main chordate groups, lancelets, tunicates, and vertebrates, leading to divergent development of olfactory receptors, eyes, hair cells and motoneurons. The lack of appropriately posited expression of certain transcription factors in lancelets and tunicates prevents them from developing vertebrate-like olfactory receptors and eyes, although they generate alternative structures for chemosensation and vision. Lancelets and tunicates lack mechanosensory cells associated with the sensation of acoustic stimuli, but have gravisensitive organs and ciliated epidermal sensory cells that may (and in some cases clearly do) provide mechanosensation and thus the capacity to respond to movement relative to surrounding water. Although functionally analogous to the vertebrate vestibular apparatus and lateral line, homology is questionable due to differences in the expression of the key transcription factors Neurog and Atoh1/7, on which development of vertebrate hair cells depends. The vertebrate hair cell-bearing inner ear and lateral line thus likely represent major evolutionary advances specific to vertebrates. Motoneurons develop in vertebrates under the control of the ventral signaling molecule hedgehog/sonic hedgehog (Hh,Shh), against an opposing inhibitory effect mediated by dorsal signaling molecules. Many elements of Shh-signaling and downstream genes involved in specifying and differentiating motoneurons are also exhibited by lancelets and tunicates, but the repertoire of MNs in vertebrates is broader, indicating greater diversity in motoneuron differentiation programs.

• Isasi, Rosario; Bentzen, Heidi Beate; Fabbri, Morris; Fuhr, Antonie; Glover, Joel Clinton & Mah, Nancy [Vis alle 10 forfattere av denne artikkelen] (2024). Dynamic governance: A new era for consent for stem cell research. Stem Cell Reports. ISSN 2213-6711. 19(9), s. 1233–1241. doi: 10.1016/j.stemcr.2024.07.006. Fulltekst i vitenarkiv Vis sammendrag

  Governance infrastructures streamline scientific and ethical provenance verification of human pluripotent stem cell (SC) lines. Yet, scientific developments (e.g., SC-derived embryo models, organoids) challenge research governance approaches to stored biospecimens, questioning the validity of informed consent (IC) models. Likewise, e-health platforms are driving major transformations in data processing, prompting a reappraisal of IC. Given these developments, participatory research platforms are identified as effective tools to promote longitudinal engagement, interactive decision-making, and dynamic governance. Learning from European initiatives piloting dynamic IC for biobanking and SC research, this Perspective explores the benefits and challenges of implementing dynamic IC and governance for SC.

• Mazzini, Letizia; Marchi, Fabiola De; Buzanska, Leonora; Follenzi, Antonia; Glover, Joel Clinton & Gelati, Maurizio [Vis alle 17 forfattere av denne artikkelen] (2024). Current status and new avenues of stem cell-based preclinical and therapeutic approaches in amyotrophic lateral sclerosis. Expert Opinion on Biological Therapy. ISSN 1471-2598. 24(9), s. 933–954. doi: 10.1080/14712598.2024.2392307. Fulltekst i vitenarkiv
• Escribá, Rubén; Beksac, Meral; Bennaceur-Griscelli, Annelise; Glover, Joel Clinton; Koskela, Satu & Latsoudis, Helen [Vis alle 8 forfattere av denne artikkelen] (2024). Submission to Stem Cells Reviews and Reports. Stem Cell Reviews and Reports (SCRR). ISSN 2629-3269. 20, s. 2155–2164. doi: 10.1007/s12015-024-10783-7. Fulltekst i vitenarkiv
• Tolstenkov, Oleg; Mikhaleva, Yana & Glover, Joel Clinton (2023). A miniaturized nigrostriatal-like circuit regulating locomotor performance in a protochordate. Current Biology. ISSN 0960-9822. 33(18), s. 3872–3883.e6. doi: 10.1016/j.cub.2023.08.015. Fulltekst i vitenarkiv Vis sammendrag

  To gain insight into the evolution of motor control systems at the origin of vertebrates, we have investigated higher-order motor circuitry in the protochordate Oikopleura dioica. We have identified a highly miniaturized circuit in Oikopleura with a projection from a single pair of dopaminergic neurons to a small set of synaptically coupled GABAergic neurons, which in turn exert a disinhibitory descending projection onto the locomotor central pattern generator. The circuit is reminiscent of the nigrostriatopallidal system in the vertebrate basal ganglia, in which disinhibitory circuits release specific movements under the modulatory control of dopamine. We demonstrate further that dopamine is required to optimize locomotor performance in Oikopleura, mirroring its role in vertebrates. A dopamine-regulated disinhibitory locomotor control circuit reminiscent of the vertebrate nigrostriatopallidal system was thus already present at the origin of ancestral chordates and has been maintained in the face of extreme nervous system miniaturization in the urochordate lineage.

• Fjerdingstad, Hege Brincker & Glover, Joel Clinton (2023). Rapid, Cost-Efficient, Enzyme-Free Passaging of Human Pluripotent Stem Cells on Feeder Cells by Ethylenediaminetetraacetic Acid-Mediated Dis-Adhesion. Journal of Visualized Experiments. 197. doi: 10.3791/63788. Fulltekst i vitenarkiv Vis sammendrag

  Human pluripotent stem cells (human embryonic stem cells, hESCs, and human induced pluripotent stem cells, hiPSCs) were originally cultured on different types of feeder cells for maintenance in an undifferentiated state in long-term culture. This approach has been supplanted to a large extent by feeder-free culture protocols, but these involve more costly reagents and can promote a transition to a primed state, which restricts the cells' differentiation capacity. In both feeder and feeder-free conditions, the harvesting of hESC or hiPSC colonies for passaging is a necessary procedure for expanding the cultures. To provide an easy and high-yield procedure for passaging hESCs/hiPSCs cultured on feeder cells, we have established a harvesting method using dis-adhesion elicited by the calcium chelator ethylenediaminetetraacetic acid (EDTA). We have assessed the yield and quality of the resultant passaged cells by comparing this approach to the original mechanical harvesting approach, in which colonies are isolated with a scalpel under a microscope (mechanical harvesting was chosen as a comparator to avoid the reagent variability associated with enzymatic harvesting). In one set of experiments, two different hESC lines were maintained on a feeder cell layer of human foreskin fibroblasts. Each line was subjected to multiple passages using EDTA-based or mechanical harvesting and assessed for colony size and morphology, cell density, stemness marker expression, differentiation to the three germ layers in embryoid bodies, and genomic aberrations. In another set of experiments, we used EDTA-based harvesting on two different hiPSC lines and obtained similar results. EDTA-induced dis-adhesion saved time and gave a higher yield of colonies of a more favorable size and more uniform morphology compared to mechanical harvesting. It was also faster than enzymatic harvesting and not prone to enzyme batch variability. The EDTA-induced dis-adhesion method also facilitates the transfer of hESC/hiPSC lines from feeder cell-based culture to feeder-free conditions if desired for downstream use and analysis.

• Hříbková, Hana; Svoboda, Ondrej; Bartecku, Elis; Zelinkova, Jana; Horinkova, Jana & Lacinova, Lubica [Vis alle 12 forfattere av denne artikkelen] (2022). Clozapine Reverses Dysfunction of Glutamatergic Neurons Derived From Clozapine-Responsive Schizophrenia Patients. Frontiers in Cellular Neuroscience. 16. doi: 10.3389/fncel.2022.830757. Fulltekst i vitenarkiv Vis sammendrag

  The cellular pathology of schizophrenia and the potential of antipsychotics to target underlying neuronal dysfunctions are still largely unknown. We employed glutamatergic neurons derived from induced pluripotent stem cells (iPSC) obtained from schizophrenia patients with known histories of response to clozapine and healthy controls to decipher the mechanisms of action of clozapine, spanning from molecular (transcriptomic profiling) and cellular (electrophysiology) levels to observed clinical effects in living patients. Glutamatergic neurons derived from schizophrenia patients exhibited deficits in intrinsic electrophysiological properties, synaptic function and network activity. Deficits in K + and Na + currents, network behavior, and glutamatergic synaptic signaling were restored by clozapine treatment, but only in neurons from clozapine-responsive patients. Moreover, neurons from clozapine-responsive patients exhibited a reciprocal dysregulation of gene expression, particularly related to glutamatergic and downstream signaling, which was reversed by c lozapine treatment. Only neurons from clozapine responders showed return to normal function and transcriptomic profile. Our results underscore the importance of K + and Na + channels and glutamatergic synaptic signaling in the pathogenesis of schizophrenia and demonstrate that clozapine might act by normalizing perturbances in this signaling pathway. To our knowledge this is the first study to demonstrate that schizophrenia iPSC-derived neurons exhibit a response phenotype correlated with clinical response to an antipsychotic. This opens a new avenue in the search for an effective treatment agent tailored to the needs of individual patients.

• Diaz, Carmen & Glover, Joel Clinton (2022). The Vestibular Column in the Mouse: A Rhombomeric Perspective. Frontiers in Neuroanatomy. 15. doi: 10.3389/fnana.2021.806815. Fulltekst i vitenarkiv Vis sammendrag

  The vestibular column is located in the hindbrain between the sensory auditory (dorsal) and trigeminal (ventral) columns, spanning rhombomeres r1 (or r2) to r9. It contains the vestibular nuclear complex that receives sensory innervation from the labyrinthine end organs in the inner ear. Gene expression studies and experimental manipulations of developmental genes, particularly Hox genes and other developmental patterning genes, are providing insight into the morphological and functional organization of the vestibular nuclear complex, particularly from a segmental standpoint. Here, we will review studies of the classical vestibular nuclei and of vestibular projection neurons that innervate distinct targets in relation to individual rhombomeres and the expression of specific genes. Studies in different species have demonstrated that the vestibular complex is organized into a hodological mosaic that relates axon trajectory and target to specific hindbrain rhombomeres and intrarhombomeric domains, with a molecular underpinning in the form of transcription factor signatures, which has been highly conserved during the evolution of the vertebrate lineage.

• Tolstenkov, Oleg; Mikhaleva, Yana & Glover, Joel Clinton (2022). Post-gastrulation transition from whole-body to tissue-specific intercellular calcium signaling in the appendicularian tunicate Oikopleura dioica. Developmental Biology. ISSN 0012-1606. 492, s. 37–46. doi: 10.1016/j.ydbio.2022.09.004. Fulltekst i vitenarkiv
• Glover, Joel Clinton & Fritzsch, Bernd (2022). Molecular mechanisms governing development of the hindbrain choroid plexus and auditory projection: A validation of the seminal observations of Wilhelm His. IBRO Neuroscience Reports. 13, s. 306–313. doi: 10.1016/j.ibneur.2022.09.011. Fulltekst i vitenarkiv Vis sammendrag

  Studies by His from 1868 to 1904 delineated the critical role of the dorsal roof plate in the development of the hindbrain choroid plexus, and of the rhombic lips in the development of hindbrain auditory centers. Modern molecular studies have confirmed these observations and placed them in a mechanistic context. Expression of the transcription factor Lmx1a/b is crucial to the development of the hindbrain choroid plexus, and also regulates the expression of Atoh1, a transcription factor that is essential for the formation of the cochlear hair cells and auditory nuclei. By contrast, development of the vestibular hair cells, vestibular ganglion and vestibular nuclei does not depend on Lmx1a/b. These findings demonstrate a common dependence on a specific gene for the hindbrain choroid plexus and the primary auditory projection from hair cells to sensory neurons to hindbrain nuclei. Thus, His’ conclusions regarding the origins of specific hindbrain structures are borne out by molecular genetic experiments conducted more than a hundred years later.

• Szabo, Attila; Akkouh, Ibrahim A.; Vandenberghe, Matthieu; Osete, Jordi Requena; Hughes, Timothy & Heine, Vivi [Vis alle 10 forfattere av denne artikkelen] (2021). A human iPSC-astroglia neurodevelopmental model reveals divergent transcriptomic patterns in schizophrenia. Translational Psychiatry. 11(1). doi: 10.1038/s41398-021-01681-4. Fulltekst i vitenarkiv Vis sammendrag

  While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In the present study, we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages critical for SCZ using RNA sequencing. The model generated astrocyte-specific gene expression patterns during differentiation that corresponded well to astroglia-specific expression signatures of in vivo cortical fetal development. Using this model we identified SCZ-specific expression dynamics, and found that SCZ-associated differentially expressed genes were significantly enriched in the medial prefrontal cortex, striatum, and temporal lobe, targeting VWA5A and ADAMTS19. In addition, SCZ astrocytes displayed alterations in calcium signaling, and significantly decreased glutamate uptake and metalloproteinase activity relative to controls. These results implicate novel transcriptional dynamics in astrocyte differentiation in SCZ together with functional changes that are potentially important biological components of SCZ pathology.

• Zeini, Darya; Glover, Joel C.; Knudsen, Kenneth Dahl & Nyström, Bo (2021). Influence of Lysine and TRITC Conjugation on the Size and Structure of Dextran Nanoconjugates with Potential for Biomolecule Delivery to Neurons. ACS Applied Bio Materials (AABM). 4(9), s. 6832–6842. doi: 10.1021/acsabm.1c00544. Fulltekst i vitenarkiv Vis sammendrag

  As a potent nonviral system for biomolecular delivery to neurons via their axons, we have studied molecular characteristics of lysinated fluorescent dextran nanoconjugates with degrees of conjugation of 0.54–15.2 mol lysine and 0.25–7.27 mol tetramethyl rhodamine isothiocyanate (TRITC) per mol dextran. We studied the influence of conjugation with lysine and TRITC on the size and structure of different molecular weight dextrans and their mobility within axons. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) experiments revealed significant differences in the size and structure of unmodified and modified dextrans. Unexpectedly, lower-molecular-weight conjugated dextrans exhibited higher molecular volumes, which we propose is due to fewer intramolecular interactions than in higher-molecular-weight conjugated dextrans. Assessment of retrograde and anterograde movement of lysine- and TRITC-conjugated dextrans in axons in the lumbar spinal cord of chicken embryos showed that lower-molecular-weight dextrans translocate more efficiently than higher-molecular-weight dextrans, despite having larger molecular volumes. This comparative characterization of different molecular weight dextrans will help define optimal features for intracellular delivery.

• Akkouh, Ibrahim; Hughes, Timothy; Steen, Vidar Martin; Glover, Joel; Andreassen, Ole Andreas & Djurovic, Srdjan [Vis alle 7 forfattere av denne artikkelen] (2021). Transcriptome analysis reveals disparate expression of inflammation-related miRNAs and their gene targets in iPSC-astrocytes from people with schizophrenia. Brain, Behavior, and Immunity. ISSN 0889-1591. 94. doi: 10.1016/j.bbi.2021.01.037. Fulltekst i vitenarkiv Vis sammendrag

  Despite the high heritability of schizophrenia (SCZ), details of its pathophysiology and etiology are still unknown. Recent findings suggest that aberrant inflammatory regulation and microRNAs (miRNAs) are involved. Here we performed a comparative analysis of the global miRNome of human induced pluripotent stem cell (iPSC)-astrocytes, derived from SCZ patients and healthy controls (CTRLs), at baseline and following inflammatory modulation using IL-1β. We identified four differentially expressed miRNAs (miR-337-3p, miR-127-5p, miR-206, miR-1185-1-3p) in SCZ astrocytes that exhibited significantly lower baseline expression relative to CTRLs. Group-specific differential expression (DE) analyses exploring possible distinctions in the modulatory capacity of IL-1β on miRNA expression in SCZ versus CTRL astroglia revealed trends toward altered miRNA expressions. In addition, we analyzed peripheral blood samples from a large cohort of SCZ patients (n = 484) and CTRLs (n = 496) screening for the expression of specific gene targets of the four DE miRNAs that were identified in our baseline astrocyte setup. Three of these genes, LAMTOR4, IL23R, and ERBB3, had a significantly lower expression in the blood of SCZ patients compared to CTRLs after multiple testing correction. We also found nominally significant differences for ERBB2 and IRAK1, which similarly displayed lower expressions in SCZ versus CTRL. Furthermore, we found matching patterns between the expressions of identified miRNAs and their target genes when comparing our in vitro and in vivo results. The current results further our understanding of the pathobiological basis of SCZ.

• Lunde, Anders & Glover, Joel C. (2020). A versatile toolbox for semi-automatic cell-by-cell object-based colocalization analysis. Scientific Reports. 10(1), s. 1–26. doi: 10.1038/s41598-020-75835-7. Fulltekst i vitenarkiv Vis sammendrag

  Differential fluorescence labeling and multi-fluorescence imaging followed by colocalization analysis is commonly used to investigate cellular heterogeneity in situ. This is particularly important when investigating the biology of tissues with diverse cell types. Object-based colocalization analysis (OBCA) tools can employ automatic approaches, which are sensitive to errors in cell segmentation, or manual approaches, which can be impractical and tedious. Here, we present a novel set of tools for OBCA using a semi-automatic approach, consisting of two ImageJ plugins, a Microsoft Excel macro, and a MATLAB script. One ImageJ plugin enables customizable processing of multichannel 3D images for enhanced visualization of features relevant to OBCA, and another enables semi-automatic colocalization quantification. The Excel macro and the MATLAB script enable data organization and 3D visualization of object data across image series. The tools are well suited for experiments involving complex and large image data sets, and can be used in combination or as individual components, allowing flexible, efficient and accurate OBCA. Here we demonstrate their utility in immunohistochemical analyses of the developing central nervous system, which is characterized by complexity in the number and distribution of cell types, and by high cell packing densities, which can both create challenging situations for OBCA.

• Glover, Joel (2020). Oikopleura. Current Biology. ISSN 0960-9822. 30(20), s. R1243–R1245. doi: 10.1016/j.cub.2020.07.075. Fulltekst i vitenarkiv
• Toch, Mathilde; Harris, Audrey; Schakman, Olivier; Kondratskaya, Elena; Dauguet, Nicolas & Boulland, Jean-Luc [Vis alle 14 forfattere av denne artikkelen] (2020). Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits. Scientific Reports. 10(996). doi: 10.1038/s41598-020-57945-4. Fulltekst i vitenarkiv Vis sammendrag

  Abstract In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut -downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2 -null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors.

• Liang, Xiao; Vatne, Guro Helén; Kristiansen, Cecilie Katrin; Ievglevskyi, Oleksandr; Kondratskaya, Elena & Glover, Joel [Vis alle 9 forfattere av denne artikkelen] (2020). N-acetylcysteine amide ameliorates mitochondrial dysfunction and reduces oxidative stress in hiPSC-derived dopaminergic neurons with POLG mutation. Experimental Neurology. ISSN 0014-4886. 337. doi: 10.1016/j.expneurol.2020.113536. Fulltekst i vitenarkiv
• Lunde, Anders & Glover, Joel Clinton (2020). A versatile toolbox for semi-automatic cell-by-cell object-based colocalization analysis. Scientific Reports. doi: 10.1038/s41598-020-75835-7. Fulltekst i vitenarkiv
• Lunde, Anders; Okaty, Benjamin W; Dymecki, Susan M & Glover, Joel (2019). Molecular profiling defines evolutionarily conserved transcription factor signatures of major vestibulospinal neuron groups. eNeuro. 6(1), s. 1–25. doi: 10.1523/ENEURO.0475-18.2019. Fulltekst i vitenarkiv Vis sammendrag

  Vestibulospinal neurons are organized into discrete groups projecting from brainstem to spinal cord, enabling vertebrates to maintain proper balance and posture. The two largest groups are the lateral vestibulospinal tract (LVST) group and the contralateral medial vestibulospinal tract (cMVST) group, with different projection lateralities and functional roles. In search of a molecular basis for these differences, we performed RNA sequencing on LVST and cMVST neurons from mouse and chicken embryos followed by immunohistofluorescence validation. Focusing on transcription factor (TF)-encoding genes, we identified TF signatures that uniquely distinguish the LVST from the cMVST group and further parse different rhombomere-derived portions comprising the cMVST group. Immunohistofluorescence assessment of the CNS from spinal cord to cortex demonstrated that these TF signatures are restricted to the respective vestibulospinal groups and some neurons in their immediate vicinity. Collectively, these results link the combinatorial expression of TFs to developmental and functional subdivisions within the vestibulospinal system.

• Lunde, Anders; Okaty, Benjamin W; Dymecki, Susan M & Glover, Joel Clinton (2019). Molecular Profiling Defines Evolutionarily Conserved Transcription Factor Signatures of Major Vestibulospinal Neuron Groups. eNeuro. doi: 10.1523/ENEURO.0475-18.2019. Fulltekst i vitenarkiv
• Glover, Joel; Aswendt, Markus; Boulland, Jean-Luc; Lojk, Jasna; Stamenković, Stefan & Andjus, Pavle [Vis alle 13 forfattere av denne artikkelen] (2019). In vivo cell tracking using non-invasive imaging of iron oxide-based particles with particular relevance for stem cell-based treatments of neurological and cardiac disease. Molecular Imaging and Biology. ISSN 1536-1632. s. 1–20. doi: 10.1007/s11307-019-01440-4. Fulltekst i vitenarkiv
• Kondratskaya, Elena; Oleksandr, Ievglevskyi; Züchner, Mark; Samara, Athina; Glover, Joel & Boulland, Jean-Luc (2019). Locomotor central pattern generator excitability states and serotonin sensitivity after spontaneous recovery from a neonatal lumbar spinal cord injury. Brain Research. ISSN 0006-8993. 1708, s. 10–19. doi: 10.1016/j.brainres.2018.12.001. Fulltekst i vitenarkiv
• Mikhaleva, Yana; Tolstenkov, Oleg & Glover, Joel (2019). Gap junction-dependent coordination of intercellular calcium signalling in the developing appendicularian tunicate Oikopleura dioica. Developmental Biology. ISSN 0012-1606. 450(1), s. 9–22. doi: 10.1016/j.ydbio.2019.03.006. Fulltekst i vitenarkiv Vis sammendrag

  We characterized spontaneous Ca2+ signals in Oikopleura dioica embryos from pre-fertilization to gastrula stages following injection of GCaMP6 mRNA into unfertilized eggs. The unfertilized egg exhibited regular, transient elevations in intracellular Ca2+ concentration with an average duration of 4–6 s and an average frequency of about 1 every 2.5 min. Fertilization was accompanied by a longer Ca2+ transient that lasted several minutes. Thereafter, regular Ca2+ transients were reinstated that spread within seconds among blastomeres and gradually increased in duration (by about 50%) and decreased in frequency (by about 20%) by gastrulation. Peak amplitudes also exhibited a dynamic, with a transitory drop occurring at about the 4-cell stage and a subsequent rise. Each peak was preceded by about 15 s by a smaller and shorter Ca2+ increase (about 5% of the main peak amplitude, average duration 3 s), which we term the “minipeak”. By gastrulation, Ca2+ transients exhibited a stereotyped initiation site on either side of the 32-64-cell embryo, likely in the nascent muscle precursor cells, and spread thereafter symmetrically in a stereotyped spatial pattern that engaged blastomeres giving rise to all the major tissue lineages. The rapid spread of the transients relative to the intertransient interval created a coordinated wave that, on a coarse time scale, could be considered an approximate synchronization. Treatment with the divalent cations Ni2+ or Cd2+ gradually diminished peak amplitudes, had only moderate effects on wave frequency, but markedly disrupted wave synchronization and normal development. The T-type Ca2+ channel blocker mibefradil similarly disrupted normal development, and eliminated the minipeaks, but did not affect wave synchronization. To assess the role of gap junctions in calcium wave spread and coordination, we first characterized the expression of two Oikopleura connexins, Od-CxA and Od-CxB, both of which are expressed during pre-gastrulation and gastrula stages, and then co-injected double-stranded inhibitory RNAs together with CGaMP6 to suppress connexin expression. Connexin mRNA knockdown led to a gradual increase in Ca2+ transient peak width, a decrease of interpeak interval and a marked disruption of wave synchronization. As seen with divalent cations and mibefradil, this desynchronization was accompanied by a disruption of normal development.

• Grimaldi, Giulia; Vagaska, Barbora; Oleksandr, Ievglevskyi; Kondratskaya, Elena; Glover, Joel & Matthews, Jason (2019). Loss of Tiparp Results in Aberrant Layering of the Cerebral Cortex. eNeuro. 6(6). doi: 10.1523/ENEURO.0239-19.2019. Fulltekst i vitenarkiv Vis sammendrag

  2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP) is an enzyme that adds a single ADP-ribose moiety to itself or other proteins. Tiparp is highly expressed in the brain; however, its function in this organ is unknown. Here, we used Tiparp–/– mice to determine Tiparp’s role in the development of the prefrontal cortex. Loss of Tiparp resulted in an aberrant organization of the mouse cortex, where the upper layers presented increased cell density in the knock-out mice compared with wild type. Tiparp loss predominantly affected the correct distribution and number of GABAergic neurons. Furthermore, neural progenitor cell proliferation was significantly reduced. Neural stem cells (NSCs) derived from Tiparp–/– mice showed a slower rate of migration. Cytoskeletal components, such as α-tubulin are key regulators of neuronal differentiation and cortical development. α-tubulin mono-ADP ribosylation (MAR) levels were reduced in Tiparp–/– cells, suggesting that Tiparp plays a role in the MAR of α-tubulin. Despite the mild phenotype presented by Tiparp–/– mice, our findings reveal an important function for Tiparp and MAR in the correct development of the cortex. Unravelling Tiparp’s role in the cortex, could pave the way to a better understanding of a wide spectrum of neurological diseases which are known to have increased expression of TIPARP.

• Skogseid, Inger Marie; Røsby, Oddveig; Konglund, Ane; Connelly, James Pattrick; Nedregaard, Bård & Jablonski, Greg Eigner [Vis alle 9 forfattere av denne artikkelen] (2018). Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation. Journal of Neurodevelopmental Disorders. 10(17), s. 1–8. doi: 10.1186/s11689-018-9235-z. Fulltekst i vitenarkiv Vis sammendrag

  Background Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally. Case presentation A 19-year-old girl with congenital mild dysmorphic facial features, cochlear implants for infant-onset deafness, and mild cognitive and emotional disability, presented with an adolescent-onset, severe generalized dystonia. Brain MRI and multiple single gene sequencing were inconclusive. Due to life-threatening dystonia, we implanted a neurostimulation device, targeting the postero-ventral internal pallidum bilaterally. The Burke-Fahn-Marsden Dystonia Rating Scale motor/disability scores improved from 87/25 to 21/13 at 2.5 months postoperatively, 26/14 at 3 years, and 30/14 at 4 years. Subsequent whole exome sequencing identified heterozygosity for the ACTB p.Arg183Trp variant. Brain imaging included 123I-ioflupane single photon emission computed tomography (Dopamine Transporter-SPECT), SPECT with 123I-epidepride (binds to dopamine type 2-receptors) and 18 Fluoro-Deoxy-Glucose (FDG)–PET. Both Epidepride-SPECT and FDG-PET showed reduced tracer uptake in the striatum bilaterally, particularly in the putamen. DaT-SPECT was slightly abnormal. Conclusions In this patient with dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity, unprecedented brain imaging findings strongly indicate striatal neuronal/dopaminergic dysfunction as the underlying cause of the dystonia. Pallidal stimulation provided a substantial improvement of the severe generalized dystonia, which is largely sustained at 4-year follow-up, and we advise this treatment to be considered in such patients. We hypothesize that the pleiotropic manifestations of the dystonia-deafness syndrome caused by this mutation derive from diverse developmental functions of beta-actin in neural crest migration and proliferation (facial dysmorphogenesis), hair cell stereocilia function (infant-onset deafness), and altered synaptic activity patterns associated with pubertal changes in striatal function (adolescent-onset dystonia). The temporal differences in developmental onset are likely due to varying degrees of susceptibility and of compensatory upregulation of other actin variants in the affected structures.

• Mazzini, Letizia; Ferrari, Daniela; Andjus, Pavle R.; Buzanska, Leonora; Cantello, Roberto & Marchi, Fabiola De [Vis alle 17 forfattere av denne artikkelen] (2018). Advances in stem cell therapy for amyotrophic lateral sclerosis. Expert Opinion on Biological Therapy. ISSN 1471-2598. 18(8), s. 865–881. doi: 10.1080/14712598.2018.1503248. Fulltekst i vitenarkiv
• Züchner, Mark; Kondratska, Olena; Sylte, Camilla; Glover, Joel & Boulland, Jean-Luc (2018). Rapid recovery and altered neurochemical dependence of locomotor central pattern generation following lumbar neonatal spinal cord injury. Journal of Physiology. ISSN 0022-3751. 596(2), s. 281–303. doi: 10.1113/JP274484. Fulltekst i vitenarkiv Vis sammendrag

  Following incomplete compression injury in the thoracic spinal cord of neonatal mice 1 day after birth (P1), we previously reported that virtually normal hindlimb locomotor function is recovered within about 3 weeks despite substantial permanent thoracic tissue loss. Here, we asked whether similar recovery occurs following lumbar injury that impacts more directly on the locomotor central pattern generator (CPG). As in thoracic injuries, lumbar injuries caused about 90% neuronal loss at the injury site and increased serotonergic innervation below the injury. Motor recovery was slower after lumbar than thoracic injury, but virtually normal function was attained by P25 in both cases. Locomotor CPG status was tested by eliciting fictive locomotion in isolated spinal cords using a widely used neurochemical cocktail (NMDA, dopamine, serotonin). No fictive locomotion could be elicited 1 day post‐injury, but could within 3 days post‐injury as readily as in age‐matched uninjured control spinal cords. Burst patterning and coordination were largely similar in injured and control spinal cords but there were differences. Notably, in both groups there were two main locomotor frequencies, but injured spinal cords exhibited a shift towards the higher frequency. Injury also altered the neurochemical dependence of locomotor CPG output, such that injured spinal cords, unlike control spinal cords, were incapable of generating low frequency rhythmic coordinated activity in the presence of NMDA and dopamine alone. Thus, the neonatal spinal cord also exhibits remarkable functional recovery after lumbar injuries, but the neurochemical sensitivity of locomotor circuitry is modified in the process.

• Lynagh, Timothy; Mikhaleva, Yana; Colding, Janne M.; Glover, Joel & Pless, Stephan A. (2018). Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 115(33), s. 8430–8435. doi: 10.1073/pnas.1806614115. Fulltekst i vitenarkiv
• Glover, Joel; Elliott, Karen L.; Erives, Albert; Chizhikov, Victor V. & Fritzsch, Bernd (2018). Wilhelm His' lasting insights into hindbrain and cranial ganglia development and evolution. Developmental Biology. ISSN 0012-1606. Published ahead of print. doi: 10.1016/j.ydbio.2018.02.001. Fulltekst i vitenarkiv
• Chawla, Rishab; Züchner, Mark; Mastrangelopoulou, Maria; Lambert, Francois Michel; Glover, Joel & Boulland, Jean-Luc (2017). Cellular reactions and compensatory tissue re-organization during spontaneous recovery after spinal cord injury in neonatal mice. Developmental Neurobiology. ISSN 1932-8451. 77(8), s. 924–946. doi: 10.1002/dneu.22479. Fulltekst i vitenarkiv Vis sammendrag

  Following incomplete spinal cord injuries, neonatal mammals display a remarkable degree of behavioral recovery. Previously, we have demonstrated in neonatal mice a wholesale re-establishment and reorganization of synaptic connections from some descending axon tracts (Boulland et al.: PLoS One 8 (2013)). To assess the potential cellular mechanisms contributing to this recovery, we have here characterized a variety of cellular sequelae following thoracic compression injuries, focusing particularly on cell loss and proliferation, inflammation and reactive gliosis, and the dynamics of specific types of synaptic terminals. Early during the period of recovery, regressive events dominated. Tissue loss near the injury was severe, with about 80% loss of neurons and a similar loss of axons that later make up the white matter. There was no sign of neurogenesis, no substantial astroglial or microglial proliferation, no change in the ratio of M1 and M2 microglia and no appreciable generation of the terminal complement peptide C5a. One day after injury the number of synaptic terminals on lumbar motoneurons had dropped by a factor of 2, but normalized by 6 days. The ratio of VGLUT1/2+ to VGAT+ terminals remained similar in injured and uninjured spinal cords during this period. By 24 days after injury, when functional recovery is nearly complete, the density of 5-HT+ fibers below the injury site had increased by a factor of 2.5. Altogether this study shows that cellular reactions are diverse and dynamic. Pronounced recovery of both excitatory and inhibitory terminals and an increase in serotonergic innervation below the injury, coupled with a general lack of inflammation and reactive gliosis, are likely to contribute to the recovery.

• Chagnaud, Boris P.; Engelmann, Jacob; Fritzsch, Bernd; Glover, Joel & Straka, Hans (2017). Sensing External and Self-Motion with Hair Cells: A Comparison of the Lateral Line and Vestibular Systems from a Developmental and Evolutionary Perspective. Brain, Behavior and Evolution. ISSN 0006-8977. 90(2), s. 98–116. doi: 10.1159/000456646. Fulltekst i vitenarkiv
• Behnan, Jinan; Stangeland, Biljana; Hosainey, Sayied Abdol Mohieb; Joel, Mrinal; Olsen, Thale Kristin & Micci, Francesca [Vis alle 9 forfattere av denne artikkelen] (2017). Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency. Oncogene. ISSN 0950-9232. 36(4), s. 570–584. doi: 10.1038/onc.2016.230. Fulltekst i vitenarkiv Vis sammendrag

  Glioblastoma Multiforme (GBM) is characterized by high cancer cell heterogeneity and the presence of a complex tumor microenvironment. Those factors are a key obstacle for the treatment of this tumor type. To model the disease in mice, the current strategy is to grow GBM cells in serum-free non-adherent condition, which maintains their tumor-initiating potential. However, the so-generated tumors are histologically different from the one of origin. In this work, we performed high-throughput marker expression analysis and investigated the tumorigenicity of GBM cells enriched under different culture conditions. We identified a marker panel that distinguished tumorigenic sphere cultures from non-tumorigenic serum cultures (high CD56, SOX2, SOX9, and low CD105, CD248, αSMA). Contrary to previous work, we found that 'mixed cell cultures' grown in serum conditions are tumorigenic and express cancer stem cell (CSC) markers. As well, 1% serum plus bFGF and TGF-α preserved the tumorigenicity of sphere cultures and induced epithelial-to-mesenchymal transition gene expression. Furthermore, we identified 12 genes that could replace the 840 genes of The Cancer Genome Atlas (TCGA) used for GBM-subtyping. Our data suggest that the tumorigenicity of GBM cultures depend on cell culture strategies that retain CSCs in culture rather than the presence of serum in the cell culture medium.

• Fritzsch, Bernd; Elliott, Karen L. & Glover, Joel (2017). Gaskell revisited: new insights into spinal autonomics necessitate a revised motor neuron nomenclature. Cell and Tissue Research. ISSN 0302-766X. 370(2), s. 195–209. doi: 10.1007/s00441-017-2676-y. Fulltekst i vitenarkiv
• Sivertsen, Magne S.; Perreault, Marie-Claude & Glover, Joel (2016). Pontine reticulospinal projections in the neonatal mouse: Internal organization and axon trajectories. Journal of Comparative Neurology. ISSN 0021-9967. 524(6), s. 1270–1291. doi: 10.1002/cne.23904. Fulltekst i vitenarkiv Vis sammendrag

  We recently characterized physiologically a pontine reticulospinal (pRS) projection in the neonatal mouse that mediates synaptic effects on spinal motoneurons via parallel uncrossed and crossed pathways (Sivertsen et al. [2014] J Neurophysiol 112:1628–1643). Here we characterize the origins, anatomical organization, and supraspinal axon trajectories of these pathways via retrograde tracing from the high cervical spinal cord. The two pathways derive from segregated populations of ipsilaterally and contralaterally projecting pRS neurons with characteristic locations within the pontine reticular formation (PRF). We obtained estimates of relative neuron numbers by counting from sections, digitally generated neuron position maps, and 3D reconstructions. Ipsilateral pRS neurons outnumber contralateral pRS neurons by threefold and are distributed about equally in rostral and caudal regions of the PRF, whereas contralateral pRS neurons are concentrated in the rostral PRF. Ipsilateral pRS neuron somata are on average larger than contralateral. No pRS neurons are positive in transgenic mice that report the expression of GAD, suggesting that they are predominantly excitatory. Putative GABAergic interneurons are interspersed among the pRS neurons, however. Ipsilateral and contralateral pRS axons have distinctly different trajectories within the brainstem. Their initial spinal funicular trajectories also differ, with ipsilateral and contralateral pRS axons more highly concentrated medially and laterally, respectively. The larger size and greater number of ipsilateral vs. contralateral pRS neurons is compatible with our previous finding that the uncrossed projection transmits more reliably to spinal motoneurons. The information about supraspinal and initial spinal pRS axon trajectories should facilitate future physiological assessment of synaptic connections between pRS neurons and spinal neurons. This is the pre-peer reviewed version of the following article: Sivertsen, M. S., Perreault, M.-C. and Glover, J. C. (2015), Pontine reticulospinal projections in the neonatal mouse: Internal organization and axon trajectories. J. Comp. Neurol., which has been published in final form at doi: 10.1002/cne.23904. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

• Falk, Anna; Heine, Vivi M.; Harwood, Adrian J.; Sullivan, Patrick F.; Peitz, Michael & Brüstle, Oliver [Vis alle 11 forfattere av denne artikkelen] (2016). Modeling psychiatric disorders: From genomic findings to cellular phenotypes. Molecular Psychiatry. ISSN 1359-4184. 21(9), s. 1167–1179. doi: 10.1038/mp.2016.89. Fulltekst i vitenarkiv Vis sammendrag

  Major programs in psychiatric genetics have identified >150 risk loci for psychiatric disorders. These loci converge on a small number of functional pathways, which span conventional diagnostic criteria, suggesting a partly common biology underlying schizophrenia, autism and other psychiatric disorders. Nevertheless, the cellular phenotypes that capture the fundamental features of psychiatric disorders have not yet been determined. Recent advances in genetics and stem cell biology offer new prospects for cell-based modeling of psychiatric disorders. The advent of cell reprogramming and induced pluripotent stem cells (iPSC) provides an opportunity to translate genetic findings into patient-specific in vitro models. iPSC technology is less than a decade old but holds great promise for bridging the gaps between patients, genetics and biology. Despite many obvious advantages, iPSC studies still present multiple challenges. In this expert review, we critically review the challenges for modeling of psychiatric disorders, potential solutions and how iPSC technology can be used to develop an analytical framework for the evaluation and therapeutic manipulation of fundamental disease processes.

• Züchner, Mark; Glover, Joel & Boulland, Jean-Luc (2016). A neonatal mouse spinal cord compression injury model. Journal of Visualized Experiments. 2016(109). doi: 10.3791/53498. Fulltekst i vitenarkiv
• Glover, Joel (2016). 3D bioprinting applications for in vitro modeling of cellular interactions and tissues. Cellular Therapy and Transplantation. ISSN 1867-416X. 5(2), s. 8–10. doi: 10.18620/1866-8836-2016-5-2-8-11. Fulltekst i vitenarkiv
• Bjørnstad, Sigrid; Samara, Athina; Erichsen, Aage; Paulsen, Ragnhild Elisabeth; Glover, Joel & Roald, Borghild (2016). Hampered lung maturation in methimazole-induced hypothyroidism in fetal chicken: morphological and molecular correlates to human fetal development. Neonatology. ISSN 1661-7800. 110(2), s. 83–92. doi: 10.1159/000444656. Fulltekst i vitenarkiv
• Lambert, Francois Michel; Bras, Hélène; Cardoit, Laura; Vinay, Laurent; Coulon, Patrice & Glover, Joel (2016). Early postnatal maturation in vestibulospinal pathways involved in neck and forelimb motor control. Developmental Neurobiology. ISSN 1932-8451. 76(10), s. 1061–1077. doi: 10.1002/dneu.22375. Fulltekst i vitenarkiv
• Joel, Mrinal; Mughal, Awais; Grieg, Zanina Zilic; Murrell, Wayne; Palmero, Sheryl & Mikkelsen, Birthe Viftrup [Vis alle 12 forfattere av denne artikkelen] (2015). Targeting PBK/TOPK decreases growth and survival of glioma initiating cells in vitro and attenuates tumor growth in vivo. Molecular Cancer. 14:121. doi: 10.1186/s12943-015-0398-x. Fulltekst i vitenarkiv Vis sammendrag

  Background Glioblastomas are invasive therapy resistant brain tumors with extremely poor prognosis. The Glioma initiating cell (GIC) population contributes to therapeutic resistance and tumor recurrence. Targeting GIC-associated gene candidates could significantly impact GBM tumorigenicity. Here, we investigate a protein kinase, PBK/TOPK as a candidate for regulating growth, survival and in vivo tumorigenicity of GICs. Methods PBK is highly upregulated in GICs and GBM tissues as shown by RNA and protein analyses. We knocked down PBK using shRNA vectors and inhibited the function of PBK protein with a pharmacological PBK inhibitor, HITOPK-032. We assessed viability, tumorsphere formation and apoptosis in three patient derived GIC cultures. Results Gene knockdown of PBK led to decreased viability and sphere formation and in one culture an increase in apoptosis. Treatment of cells with inhibitor HITOPK-032 (5 μM and 10 μM) almost completely abolished growth and elicited a large increase in apoptosis in all three cultures. HI-TOPK-032 treatment (5 mg/kg and 10 mg/kg bodyweight) in vivo resulted in diminished growth of experimentally induced subcutaneous GBM tumors in mice. We also carried out multi-culture assays of cell survival to investigate the relative effects on GICs compared with the normal neural stem cells (NSCs) and their differentiated counterparts. Normal NSCs seemed to withstand treatment slightly better than the GICs. Conclusion Our study of identification and functional validation of PBK suggests that this candidate can be a promising molecular target for GBM treatment.

• Bjørnstad, Sigrid; Austdal, Lars Peter Engeset; Roald, Borghild; Glover, Joel & Paulsen, Ragnhild Elisabeth (2015). Cracking the egg: potential of the developing chicken as a model system for nonclinical safety studies of pharmaceuticals. Journal of Pharmacology and Experimental Therapeutics. ISSN 0022-3565. 355, s. 386–396. doi: 10.1124/jpet.115.227025. Fulltekst i vitenarkiv
• Mikhaleva, Yana; Kreneisz, Orsolya; Olsen, Lisbeth Charlotte; Glover, Joel & Chourrout, Daniel (2015). Modification of the larval swimming behavior in Oikopleura dioica, a chordate with a miniaturized central nervous system by dsRNA injection into fertilized eggs. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. ISSN 1552-5007. 324(2), s. 114–127. doi: 10.1002/jez.b.22607. Fulltekst i vitenarkiv
• Kreneisz, Orsolya & Glover, Joel (2015). Developmental Characterization of Tail Movements in the Appendicularian Urochordate Oikopleura dioica. Brain, Behavior and Evolution. ISSN 0006-8977. 86(3-4), s. 191–209. doi: 10.1159/000439517. Fulltekst i vitenarkiv
• Kasumacic, Nedim; Lambert, Francois Michel; Coulon, Patrice; Bras, Hélène; Vinay, Laurent & Perreault, Marie-Claude [Vis alle 7 forfattere av denne artikkelen] (2015). Segmental organization of vestibulospinal inputs to spinal interneurons mediating crossed activation of thoracolumbar motoneurons in the neonatal mouse. Journal of Neuroscience. ISSN 0270-6474. 35(21), s. 8158–8169. doi: 10.1523/JNEUROSCI.5188-14.2015. Fulltekst i vitenarkiv
• Bonito, Maria Di; Boulland, Jean-Luc; Krezel, W; Setti, Eva; Studer, Michèle & Glover, Joel (2015). Loss of projections, functional compensation and residual deficits in the mammalian vestibulospinal system of Hoxb1-deficient mice. eNeuro. doi: 10.1523/ENEURO.0096-15.2015. Fulltekst i vitenarkiv
• Blacklaws, Jake; Deska-Gauthier, Dylan; Jones, Christopher T.; Petracca, Yanina L.; Liu, Mingwei & Zhang, Han [Vis alle 10 forfattere av denne artikkelen] (2015). Sim1 is required for the migration and axonal projections of V3 interneurons in the developing mouse spinal cord. Developmental Neurobiology. ISSN 1932-8451. 75(9), s. 1003–1017. doi: 10.1002/dneu.22266. Fulltekst i vitenarkiv
• Straka, Hans; Fritzsch, Bernd & Glover, Joel (2014). Connecting ears to eye muscles: Evolution of a 'Simple' reflex arc. Brain, Behavior and Evolution. ISSN 0006-8977. 83(2), s. 162–175. doi: 10.1159/000357833. Fulltekst i vitenarkiv
• Sivertsen, Magne S.; Glover, Joel & Perreault, Marie-Claude (2014). Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse. Journal of Neurophysiology. ISSN 0022-3077. 112(7), s. 1628–1643. doi: 10.1152/jn.00820.2013. Fulltekst i vitenarkiv
• Bjørnstad, Sigrid; Paulsen, Ragnhild Elisabeth; Erichsen, Aage; Glover, Joel & Roald, Borghild (2014). Type I and II pneumocyte differentiation in the developing fetal chicken lung: Conservation of pivotal proteins from birds to human in the struggle for life at birth. Neonatology. ISSN 1661-7800. 105(2), s. 112–120. doi: 10.1159/000355346. Fulltekst i vitenarkiv
• Boulland, Jean-Luc; Lambert, Francois Michel; Züchner, Mark; Strøm, Susanne & Glover, Joel (2013). A neonatal mouse spinal cord injury model for assessing post-injury adaptive plasticity and human stem cell integration. PLOS ONE. 8(8:e71701). doi: 10.1371/journal.pone.0071701. Fulltekst i vitenarkiv Vis sammendrag

  Despite limited regeneration capacity, partial injuries to the adult mammalian spinal cord can elicit variable degrees of functional recovery, mediated at least in part by reorganization of neuronal circuitry. Underlying mechanisms are believed to include synaptic plasticity and collateral sprouting of spared axons. Because plasticity is higher in young animals, we developed a spinal cord compression (SCC) injury model in the neonatal mouse to gain insight into the potential for reorganization during early life. The model provides a platform for high-throughput assessment of functional synaptic connectivity that is also suitable for testing the functional integration of human stem and progenitor cell-derived neurons being considered for clinical cell replacement strategies. SCC was generated at T9–T11 and functional recovery was assessed using an integrated approach including video kinematics, histology, tract tracing, electrophysiology, and high-throughput optical recording of descending inputs to identified spinal neurons. Dramatic degeneration of axons and synaptic contacts was evident within 24 hours of SCC, and loss of neurons in the injured segment was evident for at least a month thereafter. Initial hindlimb paralysis was paralleled by a loss of descending inputs to lumbar motoneurons. Within 4 days of SCC and progressively thereafter, hindlimb motility began to be restored and descending inputs reappeared, but with examples of atypical synaptic connections indicating a reorganization of circuitry. One to two weeks after SCC, hindlimb motility approached sham control levels, and weight-bearing locomotion was virtually indistinguishable in SCC and sham control mice. Genetically labeled human fetal neural progenitor cells injected into the injured spinal cord survived for at least a month, integrated into the host tissue and began to differentiate morphologically. This integrative neonatal mouse model provides opportunities to explore early adaptive plasticity mechanisms underlying functional recovery as well as the capacity for human stem cell-derived neurons to integrate functionally into spinal circuits. © 2013 Boulland et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

• Cornez, Isabelle Ann; Joel, Mrinal; Tasken, Kjetil; Langmoen, Iver Arne; Glover, Joel & Berge, Torunn (2013). EGF signalling and rapamycin-mediated mTOR inhibition in glioblastoma multiforme evaluated by phospho-specific flow cytometry. Journal of Neuro-Oncology. ISSN 0167-594X. 112(1), s. 49–57. doi: 10.1007/s11060-012-1035-9. Fulltekst i vitenarkiv
• Perreault, Marie-Claude & Glover, Joel (2013). Glutamatergic reticulospinal neurons in the mouse: developmental origins, axon projections, and functional connectivity. Annals of the New York Academy of Sciences. ISSN 0077-8923. 1279, s. 80–89. doi: 10.1111/nyas.12054. Fulltekst i vitenarkiv
• Joel, Mrinal; Sandberg, Cecilie; Boulland, Jean-Luc; Vik-Mo, Einar O.; Langmoen, Iver Arne & Glover, Joel (2013). Inhibition of tumor formation and redirected differentiation of glioblastoma cells in a xenotypic embryonic environment. Developmental Dynamics. ISSN 1058-8388. 242(9), s. 1078–1093. doi: 10.1002/dvdy.24001. Fulltekst i vitenarkiv
• Bonito, Maria Di; Glover, Joel & Studer, Michèle (2013). Hox genes and region-specific sensorimotor circuit formation in the hindbrain and spinal cord. Developmental Dynamics. ISSN 1058-8388. 242(12), s. 1348–1368. doi: 10.1002/dvdy.24055. Fulltekst i vitenarkiv
• Boulland, Jean-Luc; Mastrangelopoulou, Maria; Boqest, Andrew Craig; Jakobsen, Rune Bruhn; Noer, Agate & Glover, Joel [Vis alle 7 forfattere av denne artikkelen] (2013). Epigenetic Regulation of Nestin Expression during Neurogenic Differentiation of Adipose Tissue Stem Cells. Stem Cells and Development. ISSN 1547-3287. 22(7), s. 1042–1052. doi: 10.1089/scd.2012.0560. Fulltekst i vitenarkiv
• Nunes, Ana; Chavez-Valdez, Raul; Ezell, Tarrah; Donnelly, David F; Glover, Joel & Gauda, Estelle (2012). Effect of development on [Ca2+](i) transients to ATP in petrosal ganglion neurons: a pharmacological approach using optical recording. Journal of applied physiology. ISSN 8750-7587. 112(8), s. 1393–1402. doi: 10.1152/japplphysiol.00511.2011. Fulltekst i vitenarkiv
• Halasi, Gabor Gyorgy; Søviknes, Anne Mette; Sigurjonsson, Olafur E. & Glover, Joel (2012). Proliferation and recapitulation of developmental patterning associated with regulative regeneration of the spinal cord neural tube. Developmental Biology. ISSN 0012-1606. 365(1), s. 118–132. doi: 10.1016/j.ydbio.2012.02.012. Fulltekst i vitenarkiv
• Kasumacic, Nedim; Glover, Joel & Perreault, Marie-Claude (2012). Vestibular-mediated synaptic inputs and pathways to sympathetic preganglionic neurons in the neonatal mouse. Journal of Physiology. ISSN 0022-3751. 590(22), s. 5809–5826. doi: 10.1113/jphysiol.2012.234609. Fulltekst i vitenarkiv
• Boulland, Jean-Luc; Leung, Doreen; Thuen, Marte; Vik-Mo, Einar O.; Joel, Mrinal & Perreault, Marie-Claude [Vis alle 9 forfattere av denne artikkelen] (2012). Evaluation of Intracellular Labeling With Micron-Sized Particles of Iron Oxide (MPIOs) as a General Tool for In Vitro and In Vivo Tracking of Human Stem and Progenitor Cells. Cell Transplantation. ISSN 0963-6897. 21(8), s. 1743–1759. doi: 10.3727/096368911X627598. Fulltekst i vitenarkiv
• Szokol, Karolina; Glover, Joel & Perreault, Marie-Claude (2011). Organization of Functional Synaptic Connections between Medullary Reticulospinal Neurons and Lumbar Descending Commissural Interneurons in the Neonatal Mouse. Journal of Neuroscience. ISSN 0270-6474. 31(12), s. 4731–4742. doi: 10.1523/JNEUROSCI.5486-10.2011. Fulltekst i vitenarkiv
• Glover, Joel; Boulland, Jean-Luc; Halasi, Gabor Gyorgy & Kasumacic, Nedim (2010). Chimeric Animal Models in Human Stem Cell Biology. ILAR journal. ISSN 1084-2020. 51(1), s. 62–73. Fulltekst i vitenarkiv
• Boulland, Jean-Luc; Halasi, Gabor Gyorgy; Kasumacic, Nedim & Glover, Joel (2010). Xenotransplantation of human stem cells into the chicken embryo. Journal of Visualized Experiments. 41. doi: 10.3791/2071. Fulltekst i vitenarkiv
• Kasumacic, Nedim; Glover, Joel & Perreault, Marie-Claude (2010). Segmental patterns of vestibular-mediated synaptic inputs to axial and limb motoneurons in the neonatal mouse assessed by optical recording. Journal of Physiology. ISSN 0022-3751. 588(24), s. 4905–4925. doi: 10.1113/jphysiol.2010.195644. Fulltekst i vitenarkiv
• Fritzsch, B & Glover, Joel (2009). Structure of brains of primitive Vertebrates (tinicates, amphioxus, lampreys) and the basic features of the Vertebrate brain. I Kaas, John (Red.), Evolutionary Neuroscience. Academic Press. ISSN 9780123750808. s. 119–142. Fulltekst i vitenarkiv
• Restrepo, Carlos Ernesto; Lundfald, Line; Szabo, Gabor; Erdelyi, Ferenc; Zeilhofer, Hanns Ulrich & Glover, Joel [Vis alle 7 forfattere av denne artikkelen] (2009). Transmitter-Phenotypes of Commissural Interneurons in the Lumbar Spinal Cord of Newborn Mice. Journal of Comparative Neurology. ISSN 0021-9967. 517(2), s. 177–192. doi: 10.1002/cne.22144. Fulltekst i vitenarkiv
• Glover, Joel (2009). "THE DEVELOPMENTAL AND FUNCTIONAL LOGIC OF NEURONAL CIRCUITS": COMMENTARY ON THE KAVLI PRIZE IN NEUROSCIENCE. Neuroscience. ISSN 0306-4522. 163(4), s. 977–984. doi: 10.1016/j.neuroscience.2009.07.047. Fulltekst i vitenarkiv
• Mochida, Hiraku; Fortin, G; Champagnat, J & Glover, Joel (2009). Differential Involvement of Projection Neurons During Emergence of Spontaneous Activity in the Developing Avian Hindbrain. Journal of Neurophysiology. ISSN 0022-3077. 101(2), s. 591–602. doi: 10.1152/jn.90835.2008. Fulltekst i vitenarkiv
• Glover, Joel; Sato, K & Sato, YM (2008). Using voltage-sensitive dye recording to image the functional development of neuronal circuits in vertebrate embryos. Developmental Neurobiology. ISSN 1932-8451. 68, s. 804–816. doi: 10.1002/dneu.20629. Fulltekst i vitenarkiv
• Søviknes, Anne Mette & Glover, Joel (2008). Continued growth and cell proliferation into adulthood in the notochord of the appendicularian Oikopleura dioica. The Biological Bulletin. ISSN 0006-3185. 214(1), s. 17–28. Fulltekst i vitenarkiv
• Søviknes, Anne Mette & Glover, Joel (2008). Continued growth and cell proliferation into adulthood in the notochord of the appendicularian Oikopleura dioica. Biological Bulletin. ISSN 0898-1051. Fulltekst i vitenarkiv
• Mochida, Hiraku; Fortin, Gilles; Champagnat, Jean & Glover, Joel (2008). Differential involvement of projection neurons during emergence of spontaneous activity in the developing avian hindbrain. Journal of Neurophysiology. ISSN 0022-3077. Fulltekst i vitenarkiv
• Nissen, Ulla Vig; Moldovan, Mihail; Hounsgaard, Jørn & Glover, Joel (2008). Organization of Projection-Specific Interneurons in the Spinal Cord of the Red-Eared Turtle. Brain, Behavior and Evolution. ISSN 0006-8977. 72(3), s. 179–191. doi: 10.1159/000157355. Fulltekst i vitenarkiv
• Szokol, Karolina; Glover, Joel & Perreault, Marie-Claude (2008). Differential origin of reticulospinal drive to motoneurons innervating trunk and hindlimb muscles in the mouse revealed by optical recording. Journal of Physiology. ISSN 0022-3751. 586(21), s. 5259–5276. doi: 10.1113/jphysiol.2008.158105. Fulltekst i vitenarkiv
• Søviknes, Anne Mette & Glover, Joel (2007). Spatiotemporal patterns of neurogenesis in the appendicularian Oikopleura dioica. Developmental Biology. ISSN 0012-1606. 311(1), s. 264–275. doi: 10.1016/j.ydbio.2007.08.058. Fulltekst i vitenarkiv
• Søviknes, Anne Mette & Glover, Joel (2007). Spatiotemporal patterns of neurogenesis in the appendicularian Oikopleura dioica. Developmental Biology. ISSN 0012-1606. Fulltekst i vitenarkiv
• Søviknes, Anne Mette; Chourrout, Daniel & Glover, Joel (2007). Development of the caudal nerve cord, motoneurons, and muscle innervation in the appendicularian urochordate Oikopleura dioica. Journal of Comparative Neurology. ISSN 0021-9967. Fulltekst i vitenarkiv
• Pasqualetti, M; Diaz, C; Renaud, Jean-Sebastian; Rijli, FM & Glover, Joel (2007). Fate-mapping the mammalian hindbrain: Segmental origins of vestibular projection neurons assessed using rhombomere-specific Hoxa2 enhancer elements in the mouse. Journal of Neuroscience. ISSN 0270-6474. 27, s. 9670–9681. doi: 10.1523/JNEUROSCI.2189-07.2007. Fulltekst i vitenarkiv
• Hirsch, MR; Glover, Joel; Dufour, HD; Brunet, JF & Goridis, C (2007). Forced expression of Phox2 homeodomain transcription factors induces a branchio-visceromotor axonal phenotype. Developmental Biology. ISSN 0012-1606. 303. Fulltekst i vitenarkiv

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• Jensenius, Alexander Refsum; Glover, Joel Clinton; Upham, Finn & Guaita, Annabel Balean (2026). MusicLab Listening Body Bergen Panel Discussion. doi: https:/www.uio.no/ritmo/english/projects/musiclab/2026/listening-body-bergen/index.html. Fulltekst i vitenarkiv Vis sammendrag

  Panel discussion at the MusicLab Listening Body research concert in Bergen, where an audience with and without Parkinson's disease heard classical piano works framed by meditation and attentive listening while wearing sensor vests that recorded micromotion, breathing and heart rate, and the room was filmed with thermal video. The conversation focused on what attentive listening does to the body and brain in a concert, what the measurements can and cannot show, and what the recordings may mean for music used therapeutically by people with Parkinson's disease.

• Jensenius, Alexander Refsum; Glover, Joel Clinton; Upham, Finn & Guaita, Annabel Balean (2026). MusicLab Listening Body Oslo Panel Discussion. doi: https:/www.uio.no/ritmo/english/projects/musiclab/2026/listening-body-oslo/index.html. Fulltekst i vitenarkiv Vis sammendrag

  Panel discussion at the MusicLab Listening Body research concert in Oslo, where an audience with and without Parkinson's disease heard classical piano works framed by meditation and attentive listening while wearing sensor vests that recorded micromotion, breathing and heart rate, and the room was filmed with thermal video. The conversation focused on what attentive listening does to the body and brain in a concert, what the measurements can and cannot show, and what the recordings may mean for music used therapeutically by people with Parkinson's disease.

• To, Vu; Fjerdingstad, Hege Brincker; Lading, Helena Homme; Glover, Joel Clinton; Sigfúsdóttir, Margrét Sylvía & Chahal, Aman Singh [Vis alle 9 forfattere av denne artikkelen] (2025). Kidney organoids in an automated pipeline for safety and nephrotoxicity assessment. Fulltekst i vitenarkiv Vis sammendrag

  The key challenge for majority of organoid models is to develop organoids mature enough to recapitulate the complex organ, yet reproducible enough for reliable readouts. The use of automated robotic systems in organoid differentiation ensures precise timing and accuracy, reducing reliance on individuals and inter-laboratory variations. Here, we present approaches for miniaturizing inducible pluripotent stem cell derived kidney organoid models and discuss their applications and challenges.

• Escribá, Rubén; Beksac, Meral; Bennaceur-Griscelli, Annelise; Glover, Joel Clinton; Koskela, Satu & Latsoudis, Helen [Vis alle 8 forfattere av denne artikkelen] (2024). Correction to: Current Landscape of iPSC Haplobanks (Stem Cell Reviews and Reports, (2024), 10.1007/s12015-024-10783-7). Stem Cell Reviews and Reports (SCRR). ISSN 2629-3269. doi: 10.1007/s12015-024-10804-5. Fulltekst i vitenarkiv
• Beraneck, Mathieu; Elliott, Karen L.; Glover, Joel Clinton & Straka, Hans (2023). Editorial: Development of the vestibular system. Frontiers in Neurology. 14. doi: 10.3389/fneur.2023.1191086. Fulltekst i vitenarkiv
• Glover, Joel Clinton & Fritzsch, Bernd (2022). Corrigendum to “Molecular mechanisms governing development of the hindbrain choroid plexus and auditory projection: A validation of the seminal observations of Wilhelm His” [IBRO Neurosci. Rep. 13 (2022) 306–313, (S2667242122000732), (10.1016/j.ibneur.2022.09.011)]. IBRO Neuroscience Reports. doi: 10.1016/j.ibneur.2022.11.004. Fulltekst i vitenarkiv
• Glover, Joel Clinton; Aswendt, Markus; Boulland, Jean-Luc; Lojk, Jasna; Stamenković, Stefan & Andjus, Pavle [Vis alle 13 forfattere av denne artikkelen] (2021). Correction to: In vivo Cell Tracking Using Non-invasive Imaging of Iron Oxide-Based Particles with Particular Relevance for Stem Cell-Based Treatments of Neurological and Cardiac Disease (Molecular Imaging and Biology, (2020), 22, 6, (1469-1488), 10.1007/s11307-019-01440-4). Molecular Imaging and Biology. ISSN 1536-1632. 23(4), s. 624–624. doi: 10.1007/s11307-021-01590-4. Fulltekst i vitenarkiv
• Perreault, Marie-Claude; Bernier, Alex Pastor; Renaud, Jean-Sebastian; Roux, S. & Glover, Joel Clinton (2020). Corrigendum to “C Fragment of Tetanus Toxin Hybrid Proteins Evaluated for Muscle-specific Transsynaptic Mapping of Spinal Motor Circuitry in the Newborn Mouse” (Neuroscience (2006) 141(2) (803–816), (S0306452206004805), (10.1016/j.neuroscience.2006.04.008)). Neuroscience. ISSN 0306-4522. 424, s. 211–211. doi: 10.1016/j.neuroscience.2019.11.019. Fulltekst i vitenarkiv
• Toch, Mathilde; Harris, Audrey; Schakman, Olivier; Kondratskaya, Elena; Boulland, Jean-Luc & Dauguet, Nicolas [Vis alle 14 forfattere av denne artikkelen] (2020). Author Correction: Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits (Scientific Reports, (2020), 10, 1, (996), 10.1038/s41598-020-57945-4). Scientific Reports. 10(1). doi: 10.1038/s41598-020-70339-w. Fulltekst i vitenarkiv
• Glover, Joel; Tysnes, Ole-Bjørn; Myhr, Kjell-Morten; Bråthen, Geir; Sandvig, Ioanna & Høyer, Helle [Vis alle 9 forfattere av denne artikkelen] (2019). Hvor står ALS-forskningen i Norge? Fulltekst i vitenarkiv
• Impellizzeri, Agata Antonina Rita; Szabo, Attila; Fjerdingstad, Hege Brincker; Sullivan, Gareth; Glover, Joel & Andreassen, Ole Andreas [Vis alle 7 forfattere av denne artikkelen] (2017). Using Stem Cells to Understand the Underlying Mechanisms of Polygenic Risk of Severe Mental Disorders. Fulltekst i vitenarkiv
• Fraser, Thomas WK; Glover, Joel; Vindas, Marco A.; Øverli, Øyvind; Skjæraasen, Jon Egil & Hansen, Tom Johnny [Vis alle 8 forfattere av denne artikkelen] (2013). Does triploidy affect brain morphology and neurochemistry in Atlantic salmon, Salmo salar? Fulltekst i vitenarkiv
• Kasumacic, Nedim; Glover, Joel & Perreault, Marie-Claude (2009). Functional organization of vestibulospinal inputs to spinal motoneurons investigated with calcium imaging in the neonatal mouse. Fulltekst i vitenarkiv Vis sammendrag

  The primary function of the vestibular system is to detect accelerative forces for proper control of posture (weight support and balance) and movement. Such control occurs partly via descending projections from the vestibular nuclei to spinal motor circuits. Days before birth in rodents, vestibulospinal neurons develop axonal projections that extend to the spinal cord via the ipsilateral and contralateral medial vestibulospinal tracts (iMVST and cMVST) and the lateral vestibulospinal tract (LVST). How functional these projections are just after birth is unknown. Our goal here was to examine the organization of the vestibulospinal drive to spinal motoneurons (MNs) in a brainstem-spinal cord preparation of the neonatal mouse. Using calcium (Ca2+) imaging, we recorded responses evoked by electrical stimulation of one of the vestibular nerves in MNs throughout the spinal cord (segments C2, C6, T7, L2 and L5) in both the medial and lateral motor columns (MMC and LMC). Bilateral lesion of the MLF interrupted both MVSTs and allowed for discrimination of MVST- and LVST-mediated responses, and unilateral lesion of the MLF allowed for discrimination of iMVST- and cMVST-mediated responses. The MVSTs mediated detectable responses only in the cervical segments studied, both on the ipsilateral and contralateral sides relative to the stimulated nerve. Responses in the iMMC of C2 (there is no LMC in C2) were mediated by the iMVST alone. Responses in the iMMC of C6 derived from both the iMVST and the LVST. Responses in the iLMC of C6 were mediated by the LVST alone. All contralateral cervical responses were mediated by the cMVST alone. All responses detected in the thoracic and lumbar segments studied derived from the LVST alone. In T7, responses were evoked in both ipsi- and contralateral axial and hypaxial MNs. In both L2 and L5, responses were evoked in the iLMC, cLMC and cMMC but not the iMMC. So far our results indicate that already at birth the vestibulospinal system is functional and organized to differentially regulate activity in axial (neck and trunk) and limb MNs throughout the spinal cord in a manner similar to that seen in adult mammals. We are currently investigating the possibility that some of the responses evoked by vestibular nerve stimulation may be mediated via the medullary reticular formation.

• Søviknes, Anne Mette; Glover, Joel & Chourrout, D (2008). Mapping of the central nervous system in the urochordate Oikopleura dioica. Journal of morphology. ISSN 0362-2525. 269(12), s. 1467–1467. Fulltekst i vitenarkiv
• Glover, Joel Clinton & Lunde, Anders (2019). Transcription factor expression patterns in developing vestibulospinal neurons. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  There is a group of special neurons in the brainstem called vestibulospinal (VS) neurons that are important for the control of balance and posture of all vertebrate animals, including humans. The VS neurons receive direct sensory information from the vestibular part of the inner ear. This informs them about the current spatial orientations and movements of the head. As animals are exposed to unexpected movements and changes in posture, the VS neurons can through a quick reflex help activate spinal cord motoneurons and muscle contraction. This VS reflex is important for the maintenance of a stable and upright posture. To learn more about the mechanisms during embryonic development that leads to the generation of these unique neurons in mouse and chicken embryos, this thesis work focuses on characterizing the gene expression patterns of developing VS neurons, with an emphasis on transcription factors. By using fluorescent retrograde tracing, RNA sequencing, immunohistofluorescence, high-throughput imaging, and a custom developed microscopy image colocalization analysis tool, several expression patterns are detailed and put into an evolutionary context.

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