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4. Mertk-expressing microglia influence oligodendrogenesis and myelin modelling in the CNS.

Author

Nguyen, LT, Aprico, A, Nwoke, E, Walsh, AD, Blades, F, Avneri, R, Martin, E, Zalc, B, Kilpatrick, TJ, Binder, MD, Nguyen, LT, Aprico, A, Nwoke, E, Walsh, AD, Blades, F, Avneri, R, Martin, E, Zalc, B, Kilpatrick, TJ, and Binder, MD

Abstract

BACKGROUND: Microglia, an immune cell found exclusively within the CNS, initially develop from haematopoietic stem cell precursors in the yolk sac and colonise all regions of the CNS early in development. Microglia have been demonstrated to play an important role in the development of oligodendrocytes, the myelin producing cells in the CNS, as well as in myelination. Mertk is a receptor expressed on microglia that mediates immunoregulatory functions, including myelin efferocytosis. FINDINGS: Here we demonstrate an unexpected role for Mertk-expressing microglia in both oligodendrogenesis and myelination. The selective depletion of Mertk from microglia resulted in reduced oligodendrocyte production in early development and the generation of pathological myelin. During demyelination, mice deficient in microglial Mertk had thinner myelin and showed signs of impaired OPC differentiation. We established that Mertk signalling inhibition impairs oligodendrocyte repopulation in Xenopus tadpoles following demyelination. CONCLUSION: These data highlight the importance of microglia in myelination and are the first to identify Mertk as a regulator of oligodendrogenesis and myelin ultrastructure.

Published
2023

8. Impact d’une exposition développementale à des perturbateurs endocriniens sur le système nerveux central et la thyroïde

Author

Fini, J.B., primary, Guittonneau, C., additional, Jubin, P., additional, Salvator, M., additional, Leemans, M., additional, Martin, E., additional, Aigrot, M.S., additional, Le Mevel, S., additional, Coen, L., additional, Carre, A., additional, Demeneix, B., additional, Zalc, B., additional, Polak, M., additional, and Remaud, S., additional

Published
2021
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11. The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity.

Author

Lupu, D, Andersson, P, Bornehag, C-G, Demeneix, B, Fritsche, E, Gennings, C, Lichtensteiger, W, Leist, M, Leonards, PEG, Ponsonby, A-L, Scholze, M, Testa, G, Tresguerres, JAF, Westerink, RHS, Zalc, B, Rüegg, J, Lupu, D, Andersson, P, Bornehag, C-G, Demeneix, B, Fritsche, E, Gennings, C, Lichtensteiger, W, Leist, M, Leonards, PEG, Ponsonby, A-L, Scholze, M, Testa, G, Tresguerres, JAF, Westerink, RHS, Zalc, B, and Rüegg, J

Abstract

Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.

Published
2020

13. Contributors

Author

Airaksinen, M.S., primary, Anderson, S.A., additional, Anton, E.S., additional, Barrow, S.L., additional, Beaubien, F., additional, Belvindrah, R., additional, Ben-Ari, Y., additional, Bielle, F., additional, Boekhoorn, K., additional, Booker, A.B., additional, Borello, U., additional, Bradke, F., additional, Castellani, V., additional, Chao, M.V., additional, Charron, F., additional, Chedotal, A., additional, Cherubini, E., additional, Chisholm, A.D., additional, Cloutier, J.-F., additional, Cunningham, C.L., additional, Dalva, M.B., additional, de Castro, F., additional, Demarque, M., additional, Dickendesher, T.L., additional, Di Meglio, T., additional, Duan, Y., additional, Eavri, R., additional, Falk, J., additional, Feldheim, D.A., additional, Feller, M.B., additional, Filosa, A., additional, Flynn, K.C., additional, Foote, K.D., additional, Fukuda, A., additional, Furukawa, T., additional, Gage, F.H., additional, Gaiarsa, J.-L., additional, Garel, S., additional, Gerlitz, G., additional, Gibson, D.A., additional, Giger, R.J., additional, Griveau, A., additional, Grueber, W.B., additional, He, Z., additional, Hennig, M.H., additional, Hoogenraad, C.C., additional, Hübner, C.A., additional, Izzi, L., additional, Jeanneteau, F., additional, Kerschensteiner, D., additional, Klein, R., additional, Komuro, H., additional, Komuro, Y., additional, Kriegstein, A.R., additional, Kumada, T., additional, Leslie, J.H., additional, Li, G., additional, Llano, O., additional, Lledo, P.-M., additional, Lohmann, C., additional, LoTurco, J.J., additional, Lu, C.S., additional, Ludwig, A., additional, Luhmann, H.J., additional, Ma, L., additional, Le Marchand, S.J., additional, Martin, T.C., additional, McAllister, A.K., additional, McNeal, D., additional, Mizrahi, A., additional, Moya, F., additional, Munz, M., additional, Nakajima, K., additional, Nakanishi, Y., additional, Nedivi, E., additional, Nelson, S.B., additional, Noctor, S.C., additional, Nudo, R.J., additional, Ohno, N., additional, Okaty, B.W., additional, Petros, T.J., additional, Pfeffer, C.K., additional, Pierani, A., additional, Pleasure, S.J., additional, Polleux, F., additional, Prince, J.E.A., additional, Reiner, O., additional, Ribera, A.B., additional, Rijli, F.M., additional, Rivera, C., additional, Ruthazer, E.S., additional, Salinas, P.C., additional, Scheiffele, P., additional, Schreiner, D., additional, Sekine, K., additional, Sernagor, E., additional, Sigrist, S.J., additional, Sotelo, C., additional, Spitzer, N.C., additional, Stanco, A., additional, Stiess, M., additional, Suzuki, S.C., additional, Tabata, H., additional, Toni, N., additional, Uvarov, P., additional, Valdeolmillos, M., additional, Van Vactor, D., additional, Vinay, L., additional, Wang, F., additional, Wichmann, C., additional, Wong, R.O.L., additional, Yoshimatsu, T., additional, Zalc, B., additional, and Zhao, C., additional

Published
2013
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19. Kazuhiro Ikenaka (1952-2018) OBITUARY

Author

Wanaka, A, Lawrence, AJ, Yoneda, Y, Zalc, B, Stadlin, A, Maria Pasquini, J, Beart, PM, Wanaka, A, Lawrence, AJ, Yoneda, Y, Zalc, B, Stadlin, A, Maria Pasquini, J, and Beart, PM

Abstract

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Published
2019

29. Myelination

Author

Salzer, J.L., Zalc, B., New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Neural Conduction, Biological Evolution, Nerve Fibers, Myelinated, General Biochemistry, Genetics and Molecular Biology, Axons, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, nervous system, Vertebrates, Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Myelin Sheath
Abstract

International audience; Myelin is a key evolutionary acquisition that underlay the development of the large, complex nervous systems of all hinged-jaw vertebrates. By promoting rapid, efficient nerve conduction, myelination also made possible the development of the large body size of these vertebrates. In addition to increasing the speed of nerve conduction, myelination has emerged as a source of plasticity in neural circuits that is crucial for proper timing and function. Here, we briefly describe the organization of myelin and of myelinated axons, as well as the functions of myelin in nerve conduction and neural circuits, and consider its potential evolutionary origins.

Published
2016

31. Early Specification of Oligodendrocytes in the Chick Embryonic Brain

Author

Villegas, E. M. Perez, Olivier, C., Spassky, N., Poncet, C., Cochard, P., Zalc, B., Thomas, J-L., and Martinez, S.

Subjects
Developmental biology -- Research, Myelin proteins -- Research, Cell research -- Analysis, Biological sciences
Abstract

Oligodendrocytes are the myelin-forming cells in the central nervous system of vertebrates. In the rodent embryo, these cells have been shown to emerge from restricted territories of the neuroepithelium. However, a comprehensive view of the development of oligodendroglial populations from their ventricular sources remains to be established. As a first step toward this aim, we have examined in vivo the spatiotemporal emergence of oligodendrocytes in the chick embryonic brain. We have detailed the patterns of expression of three early markers of the oligodendroglial lineage: the plp/dm-20 and PDGFR[Alpha] transcripts and the O4-reactive antigen. During embryonic development, these molecules showed a similar segmental pattern of expression. However, plp/dm-[20.sup.+] cells were already observed, in the ventricular layer, at E2.5, i.e., 2 days before the appearance of [O4.sup.+] and PDGFR[[Alpha].sup.+] cells, suggesting that oligodendrocyte precursors arise nearly simultaneously with neurons. In the chick embryonic brain, the onset of expression of plp/dm-20 appears therefore to be the earliest event indicative of oligodendroglial specification and we propose, based on the expression of plp/dm-20 transcript, a ventricular map of the foci at which oligodendrocytes originate. In addition, we document the precocious segregation, from E5, of plp/dm-[20.sup.+] and PDGFR[[Alpha].sup.+] oligodendroglial cells in the subventricular and mantle layers of the brain. [C] 1999 Academic Press Key Words: oligodendrocyte; early specification; plp/dm-[20.sup.+] precursors; neural tube regionalization; myelin.

Published
1999

34. The origin of the myelination programm in vertebrates

Author

Zalc, B., Goujet, D., Colman, D., CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paléobiodiversité et paléoenvironnements, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
[SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2008

37. Oligodendrocyte devekopment in the embryonic brain: contribution of the plp lineage

Author

Le Bras, B., Chatzopoulou, E., Haydon, K., Martinez, S., Ikenaka, K., Prestoz, L., Spassky, N., Zalc, B., Thomas, Jean-Louis, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), and Raymond, Guy

Subjects
PASCAL, embryon, biologie du développement, cellule, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, système nerveux, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Published
2005

38. Evaluation of hematopoietic potential generated by transplantation of muscle-derived stem cells in mice

Author

Prestoz, L., Badaoui, S., Guillier, M., Haoud, C., Opolon, P., Thomas, Jean-Louis, Zalc, B., Vainchenker, W., Turban, Ag, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), and Raymond, Guy

Subjects
PASCAL, biologie du développement, differenciation cellulaire, cellule, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Published
2004

39. control of axonophilic migration of oligodendrocyte precursor cells by Eph-ephrin interaction

Author

Prestoz, L., Chatzopoulo, E., Lemkine, G., Spassky, N., Lebras, B., Kagawa, T., Ikenaka, K., Zalc, B., Thomas, Jean-Louis, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), and Raymond, Guy

Subjects
PASCAL, embryon, biologie du développement, cellule, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, système nerveux, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Published
2004

40. Human medulloblastoma cell line DEV is a potent tool to screen for factors influencing differentiation of neural stem cells

Author

Buzanska, L., Spassky, N., Belin, M.F., Giangrande, A., Guillemot, F., Klämbt, C., Labouesse, M., Thomas, J.L., Domanska-Janik, K., Zalc, B., Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2001

41. RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao

Author

Traver, I, Bidot, B, Spassky, N., Baltauss, B, de Tand, M, Thomas, J, Zalc, B., Janoueix-Lerosey, J, Gunzburg, J, Institut Curie [Paris], Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Binding Sites, Base Sequence, Sequence Homology, Amino Acid, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Heterotrimeric GTP-Binding Proteins, Recombinant Proteins, GTP Phosphohydrolases, Mice, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, sense organs, Amino Acid Sequence, RNA, Messenger, RGS Proteins, DNA Primers, HeLa Cells, Research Article
Abstract

International audience; In an attempt to elucidate the physiological function(s) of the Ras-related Rap proteins, we used the yeast two-hybrid system and isolated a cDNA encoding a protein that interacts with both Rap1 and Rap2, but not with Ras; the use of Rap2 mutants showed that this interaction is characteristic of a potential Rap effector. This protein was identified as RGS14, a member of the recently discovered family of RGS ('regulators of G-protein signalling') proteins that stimulate the GTPase activity of the GTP-binding alpha subunit of heterotrimeric G-proteins (Galpha). Deletion analysis, as well as in vitro binding experiments, revealed that RGS14 binds Rap proteins through a domain distinct from that carrying the RGS identity, and that this domain shares sequence identity with the Ras/Rap binding domain of B-Raf and Raf-1 kinases. RGS14 is distinguished from other RGS proteins by its marked preference for Galpha(o) over other Galpha subunits: RGS14 binds preferentially to Galpha(o) in isolated brain membranes, and also interacts preferentially with Galpha(o) (as compared with Galpha(i1)) to stimulate its GTPase activity. In adult mice, RGS14 expression is restricted to spleen and brain. In situ hybridization studies showed that it is highly expressed only in certain areas of mouse brain (such as the CA1 and CA2 regions of the hippocampus), and that this pattern closely resembles that of Rap2, but not Rap1, expression. Double in situ hybridization experiments revealed that certain cells in the hippocampus express both RGS14 and Galpha(o), as well as both RGS14 and Rap2, showing that the interaction of RGS14 with Galpha(o) and Rap2 is physiologically possible. Taken together, these results suggest that RGS14 could constitute a bridging molecule that allows cross-regulation of signalling pathways downstream from G-protein-coupled receptors involving heterotrimeric proteins of the G(i/o) family and those involving the Ras-related GTPase Rap2.

Published
2000

42. Ascl1/Mash1 Promotes Brain Oligodendrogenesis during Myelination and Remyelination

Author

Nakatani, H., primary, Martin, E., additional, Hassani, H., additional, Clavairoly, A., additional, Maire, C. L., additional, Viadieu, A., additional, Kerninon, C., additional, Delmasure, A., additional, Frah, M., additional, Weber, M., additional, Nakafuku, M., additional, Zalc, B., additional, Thomas, J.-L., additional, Guillemot, F., additional, Nait-Oumesmar, B., additional, and Parras, C., additional

Published
2013
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44. Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype.

Author

Rauschka, H., Colsch, B., Baumann, N., Wevers, R.A., Schmidbauer, M., Krammer, M., Turpin, J.C., Lefevre, M., Olivier, C., Tardieu, S., Krivit, W., Moser, H., Moser, A., Gieselmann, V., Zalc, B., Cox, T., Reuner, U., Tylki-Szymanska, A., Aboul-Enein, F., LeGuern, E., Bernheimer, H., Berger, J., Rauschka, H., Colsch, B., Baumann, N., Wevers, R.A., Schmidbauer, M., Krammer, M., Turpin, J.C., Lefevre, M., Olivier, C., Tardieu, S., Krivit, W., Moser, H., Moser, A., Gieselmann, V., Zalc, B., Cox, T., Reuner, U., Tylki-Szymanska, A., Aboul-Enein, F., LeGuern, E., Bernheimer, H., and Berger, J.

Abstract

Contains fulltext : 49461.pdf (publisher's version ) (Closed access), BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity. OBJECTIVE: To search for genotype-phenotype correlations in late-onset MLD. METHODS: The authors reviewed the clinical course of 22 patients homozygous for mutation P426L vs 20 patients heterozygous for mutation I179S, in which the second arylsulfatase A (ASA) mutation had also been determined. RESULTS: P426L homozygotes principally presented with progressive gait disturbance caused by spastic paraparesis or cerebellar ataxia; mental disturbance was absent or insignificant at the onset of disease but became more apparent as the disease evolved. In contrast, compound heterozygotes for I179S presented with schizophrenia-like behavioral abnormalities, social dysfunction, and mental decline, but motor deficits were scarce. Reduced peripheral nerve conduction velocities and less residual ASA activity were present in P426L homozygotes vs I179S heterozygotes. CONCLUSION: The characteristic clinical differences between homozygous P426L and compound heterozygous I179S patients establish a distinct genotype-phenotype correlation in late-onset metachromatic leukodystrophy.

Published
2006

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