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2. Author Correction: Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes

Author

Lehman, Norman L., Spassky, Nathalie, Sak, Müge, Webb, Amy, Zumbar, Cory T., Usubalieva, Aisulu, Alkhateeb, Khaled J., McElroy, Joseph P., Maclean, Kirsteen H., Fadda, Paolo, Liu, Tom, Gangalapudi, Vineela, Carver, Jamie, Abdullaev, Zied, Timmers, Cynthia, Parker, John R., Pierson, Christopher R., Mobley, Bret C., Gokden, Murat, Hattab, Eyas M., Parrett, Timothy, Cooke, Ralph X., Lehman, Trang D., Costinean, Stefan, Parwani, Anil, Williams, Brian J., Jensen, Randy L., Aldape, Kenneth, and Mistry, Akshitkumar M.

Published
2023
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5. Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes

Author

Lehman, Norman L., Spassky, Nathalie, Sak, Müge, Webb, Amy, Zumbar, Cory T., Usubalieva, Aisulu, Alkhateeb, Khaled J., McElroy, Joseph P., Maclean, Kirsteen H., Fadda, Paolo, Liu, Tom, Gangalapudi, Vineela, Carver, Jamie, Abdullaev, Zied, Timmers, Cynthia, Parker, John R., Pierson, Christopher R., Mobley, Bret C., Gokden, Murat, Hattab, Eyas M., Parrett, Timothy, Cooke, Ralph X., Lehman, Trang D., Costinean, Stefan, Parwani, Anil, Williams, Brian J., Jensen, Randy L., Aldape, Kenneth, and Mistry, Akshitkumar M.

Published
2022
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10. Airway ciliated cells in adult lung homeostasis and COPD

Author

Petit, Laure M.G., primary, Belgacemi, Randa, additional, Ancel, Julien, additional, Saber Cherif, Lynda, additional, Polette, Myriam, additional, Perotin, Jeanne-Marie, additional, Spassky, Nathalie, additional, Pilette, Charles, additional, Al Alam, Denise, additional, Deslée, Gaëtan, additional, and Dormoy, Valérian, additional

Published
2023
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15. CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signaling to promote expansion of cortical progenitors.

Author

Vanderhaegen, Pierre, Abramowicz, Marc, Mc Entee, Kathleen, Wittamer, Valérie, Naeije, Gilles, Bellefroid, Eric, SPASSKY, Nathalie NS, Berninger, F., Van Heurck, Roxane, Vanderhaegen, Pierre, Abramowicz, Marc, Mc Entee, Kathleen, Wittamer, Valérie, Naeije, Gilles, Bellefroid, Eric, SPASSKY, Nathalie NS, Berninger, F., and Van Heurck, Roxane

Abstract

Le développement et l’évolution du cerveau humain sont depuis longtemps des sujets d’études fascinants, et d’autant plus depuis quelques années par l’avancée des données génomiques, transcriptomiques, et des modèles d’études disponibles. Durant ce projet, je me suis focalisée sur CROCCP2, un gène spécifique à la lignée des hominidés qui est apparu durant l’évolution a partir d’une duplication partielle du gène ancestral CROCC (Ciliary Rootlet Coiled Coil), aussi appelé rootletin. CROCC est le composant majeur du ciliary rootlet, un organelle dont le role est encore très mal connu, situé a la base du cil primaire. Au cours de cette étude nous avons découvert que CROCCP2 est exprimé fortement au cours du développement cortical humain mais pas au cours du développement cortical des autres primates. Le gain de fonction de CROCCP2 au cours de la corticogenèse murine in vivo est associé avec une réduction de la ciliogenèse, une hyper-activation de la voie mTOR, et une augmentation de la taille des cellules de glie radiaire, qui ont pour conséquence une amplification des progéniteurs corticaux et de la neurogenèse. L’action de CROCCP2 sur la dynamique ciliaire et la neurogenèse implique l’inhibition de IFT20, une protéine impliquée dans le transport ciliaire. De plus nous avons obtenu des données préliminaires suggérant que CROCCP2 est actif au cours de la corticogenèse humaine.En conclusion nous avons identifié une protéine présente dans le cortex humain ayant un rôle majeur dans l’expansion des progéniteurs corticaux via la modulation de la dynamique ciliaire ., Doctorat en Sciences médicales (Médecine), info:eu-repo/semantics/nonPublished

Published
2022

18. Centriole amplification by mother and daughter centrioles differs in multiciliated cells

Author

Jord, Adel Al, Lemaitre, Anne-Iris, Delgehyr, Nathalie, Faucourt, Marion, Spassky, Nathalie, and Meunier, Alice

Subjects
Cell research, Centrioles -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The semi-conservative centrosome duplication in cycling cells gives rise to a centrosome composed of a mother and a newly formed daughter centriole (1). Both centrioles are regarded as equivalent in their ability to form new centrioles and their symmetric duplication is crucial for cell division homeostasis (2-4). Multiciliated cells do not use the archetypal duplication program and instead form more than a hundred centrioles that are required for the growth of motile cilia and the efficient propelling of physiological fluids (5). The majority of these new centrioles are thought to appear denovo, that is, independently from the centrosome, around electron-dense structures called deuterosomes (6-8). Their origin remains unknown. Using live imaging combined with correlative super-resolution light and electron microscopy, we show that all new centrioles derive from the pre-existing progenitor cell centrosome through multiple rounds of procentriole seeding. Moreover, we establish that only the daughter centrosomal centriole contributes to deuterosome formation, and thus to over ninety per cent of the final centriole population. This unexpected centriolar asymmetry grants new perspectives when studying cilia-related diseases (5,9) and pathological centriole amplification observed in cycling cells and associated with microcephaly and cancer (2-4,10)., Large-scale centriole production in multiciliated cells is thought to occur through two independent pathways: a commonly described 'de novo' pathway, also known as the acentriolar/deuterosome pathway; and a centriolar pathway, [...]

Published
2014

19. Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease

Author

Keryer, Guy, Pineda, Jose R., Liot, Geraldine, Kim, Jinho, Dietrich, Paula, Benstaali, Caroline, Smith, Karen, Cordelieres, Fabrice P., Spassky, Nathalie, Ferrante, Robert J., Dragatsis, Ioannis, and Saudou, Frederic

Subjects
Cilia and ciliary motion -- Growth -- Genetic aspects, Huntington's chorea -- Diagnosis -- Care and treatment, Genetic regulation -- Research, Company growth, Health care industry
Abstract

Huntington disease (HD) is a devastating autosomal-dominant neurodegenerative disorder. It is caused by expansion of a CAG repeat in the first exon of the huntingtin (HTT) gene that encodes a [...]

Published
2011
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22. GemC1 is a critical switch for neural stem cell generation in the postnatal brain

Author

Lalioti, Maria-Eleni, Kaplani, Konstantina, Lokka, Georgia, Georgomanolis, Theodore, Kyrousi, Christina, Dong, Weilai, Dunbar, Ashley, Parlapani, Evangelia, Dannianidou, Eleni, Spassky, Nathalie, Kahle, Kristopher T., Papantonis, Argyris, Lygerou, Zoi, Taraviras, Stavros, Lalioti, Maria-Eleni, Kaplani, Konstantina, Lokka, Georgia, Georgomanolis, Theodore, Kyrousi, Christina, Dong, Weilai, Dunbar, Ashley, Parlapani, Evangelia, Dannianidou, Eleni, Spassky, Nathalie, Kahle, Kristopher T., Papantonis, Argyris, Lygerou, Zoi, and Taraviras, Stavros

Abstract

The subventricular zone (SVZ) is one of two main niches where neurogenesis persists during adulthood, as it retains neural stem cells (NSCs) with self-renewal capacity and multi-lineage potency. Another critical cellular component of the niche is the population of postmitotic multiciliated ependymal cells. Both cell types are derived from radial glial cells that become specified to each lineage during embryogenesis. We show here that GemC1, encoding Geminin coiled-coil domain-containing protein 1, is associated with congenital hydrocephalus in humans and mice. Our results show that GemC1 deficiency drives cells toward a NSC phenotype, at the expense of multiciliated ependymal cell generation. The increased number of NSCs is accompanied by increased levels of proliferation and neurogenesis in the postnatal SVZ. Finally, GemC1-knockout cells display altered chromatin organization at multiple loci, further supporting a NSC identity. Together, these findings suggest that GemC1 regulates the balance between NSC generation and ependymal cell differentiation, with implications for the pathogenesis of human congenital hydrocephalus.

Published
2019

23. Ependymal cilia beating induces an actin network to protect centrioles against shear stress

Author

Mahuzier, Alexia, Shihavuddin, Asm, Fournier, Clémence, Lansade, Pauline, Faucourt, Marion, Menezes, Nikita, Meunier, Alice, Garfa-Traoré, Meriem, Carlier, Marie-France, Voituriez, Raphael, Genovesio, Auguste, Spassky, Nathalie, Delgehyr, Nathalie, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), 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)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (LJP), Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Théorique de la Matière Condensée (LPTMC), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), ANR-12-BSV4-0006,CiliaStem,Etude de la fonction des cils au cours de la neurogenèse chez les mammifères(2012), European Project: 647466,H2020,ERC-2014-CoG,EDeN(2015), European Project: 249982,EC:FP7:ERC,ERC-2009-AdG,FORCEFULACTIN(2010), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE - - Amidex2011 - ANR-11-IDEX-0001 - IDEX - VALID, BLANC - Etude de la fonction des cils au cours de la neurogenèse chez les mammifères - - CiliaStem2012 - ANR-12-BSV4-0006 - BLANC - VALID, Ependymal cell Development: New insight into neurological diseases - EDeN - - H20202015-12-01 - 2020-11-30 - 647466 - VALID, and Coordinated regulation of actin dynamics in cell motility and morphogenesis : from molecules to reconstituted biomimetic assays - FORCEFULACTIN - - EC:FP7:ERC2010-05-01 - 2015-10-31 - 249982 - VALID

Subjects
Mice, Knockout, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Science, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Microfilament Proteins, Models, Neurological, Proteins, Mice, Transgenic, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], macromolecular substances, respiratory system, Article, Actins, Biomechanical Phenomena, Cytoskeletal Proteins, Mice, Ependyma, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, lcsh:Q, Cilia, Protein Interaction Maps, lcsh:Science, Centrioles
Abstract

Multiciliated ependymal cells line all brain cavities. The beating of their motile cilia contributes to the flow of cerebrospinal fluid, which is required for brain homoeostasis and functions. Motile cilia, nucleated from centrioles, persist once formed and withstand the forces produced by the external fluid flow and by their own cilia beating. Here, we show that a dense actin network around the centrioles is induced by cilia beating, as shown by the disorganisation of the actin network upon impairment of cilia motility. Moreover, disruption of the actin network, or specifically of the apical actin network, causes motile cilia and their centrioles to detach from the apical surface of ependymal cell. In conclusion, cilia beating controls the apical actin network around centrioles; the mechanical resistance of this actin network contributes, in turn, to centriole stability., Ependymal ciliary beating contributes to the flow of cerebrospinal fluid in the brain ventricles and these cilia resist the flow forces. Here the authors show that the assembly of a dense actin network around the centrioles is induced by cilia beating to protect centrioles against the shear stress generated by ciliary motility.

Published
2018
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24. Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases

Author

Kelley Matthew, Dabdoub Alain, Qian Dong, Spassky Nathalie, Chen Ping, Vivancos Valérie, Studer Michèle, and Guthrie Sarah

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM) neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP) pathway in this process. Results Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudalhigh to rostrallow gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins. Conclusion These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.

Published
2009
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25. FastSME: faster and smoother manifold extraction from 3D stack

Author

Basu, Sreetama, Rexhepaj, Elton, Spassky, Nathalie, Genovesio, Auguste, Paulsen, Rasmus Reinhold, Shihavuddin, ASM, Basu, Sreetama, Rexhepaj, Elton, Spassky, Nathalie, Genovesio, Auguste, Paulsen, Rasmus Reinhold, and Shihavuddin, ASM

Published
2018

26. Smooth 2D manifold extraction from 3D image stack

Author

Shihavuddin, Asm, primary, Basu, Sreetama, additional, Rexhepaj, Elton, additional, Delestro, Felipe, additional, Menezes, Nikita, additional, Sigoillot, Séverine M, additional, Del Nery, Elaine, additional, Selimi, Fekrije, additional, Spassky, Nathalie, additional, and Genovesio, Auguste, additional

Published
2017
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28. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis

Author

Boulay, Anne- Cécile, Saubaméa, Bruno, Adam, Nicolas, Chasseigneaux, Stéphanie, Mazaré, Noémie, Gilbert, Alice, Bahin, Mathieu, Bastianelli, Leila, Blugeon, Corinne, Perrin, Sandrine, Pouch, Juliette, Ducos, Bertrand, Le Crom, Stéphane, Chretien, Fabrice, Declèves, Xavier, Laplanche, Jean-Louis, Cohen-Salmon, Martine, Foerster, Philippe, Daclin, Marie, Asm, Shihavuddin, Faucourt, Marion, Boletta, Alessandra, Genovesio, Auguste, Spassky, Nathalie, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Statistique de l'ENS (LPS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Division of Genetics and Cell Biology Dibit San Raffaele Scientific Institute, Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IRCCS San Raffaele Scientific Institute [Milan, Italie], We acknowledge the IBENS Imaging Facility, member of the national infrastructure France-BioImaging, supported by the French National Research Agency (ANR-10- INBS-04, ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL* Research University Investments for the future) and by the ’Région Ile-de-France’ (NERF N° 2011-45, DIM Cerveau et Pensée ’Alpins’), the Fondation pour la Recherche Médicale (N° DGE 20111123023) and the Fédération pour la Recherche sur le Cerveau - Rotary International France (2011). The N.S. laboratory was financed by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Centre National de la Recherche Scientifique (CNRS), the Ecole Normale Supérieure (ENS), the ANR (ANR-12-BSV4-0006), the European Research Council (ERC Consolidator grant 647466), the Fondation pour la Recherche Médicale (FRM20140329547) the Canceropole-IDF (2014-1-PL BIO-11-INSERM 12-1) and the Fondation Pierre-Gilles de Gennes (FPGG03). It was supported by the program ‘Investissements d’Avenir’ of the French Government and implemented by the ANR (ANR-10-LABX-54 MEMOLIFE and ANR-11-IDEX-0001-02 PSL* Research University). P.F. and M.D. were supported by a doctoral grant from Sorbonne Universités and by the MEMO LIFE program (P.F.). Deposited in PMC for immediate release., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), Bahin, Mathieu, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE - - Amidex2011 - ANR-11-IDEX-0001 - IDEX - VALID, École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL)

Subjects
0301 basic medicine, [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing, Neurogenesis, Morphogenesis, Mice, Transgenic, Mechanistic Target of Rapamycin Complex 1, Biology, Cerebral Ventricles, Mice, 03 medical and health sciences, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Pregnancy, mTORC1 pathway, Animals, Cilia, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Brain Ventricle, Neurons, Sirolimus, TOR Serine-Threonine Kinases, Cilium, Embryogenesis, Brain, Cell Polarity, Cell Biology, Anatomy, Stem Cells and Regeneration, Embryo, Mammalian, Embryonic stem cell, Cell biology, Spindle apparatus, Mice, Inbred C57BL, Ventricular system, 030104 developmental biology, Multiprotein Complexes, Cerebral ventricle, Female, Hydrocephalus, Signal Transduction, Developmental Biology
Abstract

Radial glial cells (RCGs) are self-renewing progenitor cells that give rise to neurons and glia during embryonic development. Throughout neurogenesis, these cells contact the cerebral ventricles and bear a primary cilium. Although the role of the primary cilium in embryonic patterning has been studied, its role in brain ventricular morphogenesis is poorly characterized. Using conditional mutants, we show that the primary cilia of radial glia determine the size of the surface of their ventricular apical domain through regulation of the mTORC1 pathway. In cilium-less mutants, the orientation of the mitotic spindle in radial glia is also significantly perturbed and associated with an increased number of basal progenitors. The enlarged apical domain of RGCs leads to dilatation of the brain ventricles during late embryonic stages (ventriculomegaly), which initiates hydrocephalus during postnatal stages. These phenotypes can all be significantly rescued by treatment with the mTORC1 inhibitor rapamycin. These results suggest that primary cilia regulate ventricle morphogenesis by acting as a brake on the mTORC1 pathway. This opens new avenues for the diagnosis and treatment of hydrocephalus., Highlighted article: Primary cilia regulate ventricle morphogenesis in mice by modulating the mTORC1 pathway, highlighting a new role for mTOR signalling during brain development.

Published
2017
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32. Phosphoinositides regulation and function in the ciliary compartment of Neural stem cells and Ependymal cells

Author

Schiffmann, Serge N., Vassart, Gilbert, Erneux, Christophe, Vanderhaeghen, Pierre, Pochet, Roland, SPASSKY, Nathalie NS, Tissir, Fadel, Chavez Garcia, Edison, Schiffmann, Serge N., Vassart, Gilbert, Erneux, Christophe, Vanderhaeghen, Pierre, Pochet, Roland, SPASSKY, Nathalie NS, Tissir, Fadel, and Chavez Garcia, Edison

Abstract

This thesis describes the work that I have carried out in the Laboratory of Neurophysiolgy at the Université Libre de Bruxelles, under the supervision of Prof. Serge Schiffmann, in collaboration with Prof. Stéphane Schurmans of Université of Liège.The work is divided in two distinct but related projects and the results section is thus divided into two main chapters. The results described are presented in the form of two manuscripts, the first chapter is named “Ciliary phosphoinositides regulation by INPP5E controls Shh signaling by allowing trafficking of Gpr161 in neural stem cells primary cilium”.The second is named “Regulation of phosphoinositides ciliary levels controls trafficking and ciliogenesis in ependymal cells”.Since both manuscripts are comprehensive regarding the results, and methods, these are inserted as such into the thesis.An expanded introduction to the field, placing the results into context, precedes these two chapters. An extended discussion section follows each chapter; it presents some elements of discussion not included in the manuscripts, the implications of the results and the scope for further research., Doctorat en Sciences biomédicales et pharmaceutiques, info:eu-repo/semantics/nonPublished

Published
2014

34. [Pinwheel architecture of neural stem cell niche, the third dimension]

Author

Spassky, Nathalie, Caillé, Isabelle, Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie des processus adaptatifs (NPA), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SCCO.NEUR]Cognitive science/Neuroscience, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2009

35. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis.

Author

Foerster, Philippe, Daclin, Marie, Asm, Shihavuddin, Faucourt, Marion, Boletta, Alessandra, Genovesio, Auguste, and Spassky, Nathalie

Subjects
NEUROGLIA, MTOR protein, EMBRYOLOGY
Abstract

Radial glial cells (RCGs) are self-renewing progenitor cells that give rise to neurons and glia during embryonic development. Throughout neurogenesis, these cells contact the cerebral ventricles and bear a primary cilium. Although the role of the primary cilium in embryonic patterning has been studied, its role in brain ventricular morphogenesis is poorly characterized. Using conditional mutants, we show that the primary cilia of radial glia determine the size of the surface of their ventricular apical domain through regulation of the mTORC1 pathway. In cilium-less mutants, the orientation of the mitotic spindle in radial glia is also significantly perturbed and associated with an increased number of basal progenitors. The enlarged apical domain of RGCs leads to dilatation of the brain ventricles during late embryonic stages (ventriculomegaly), which initiates hydrocephalus during postnatal stages. These phenotypes can all be significantly rescued by treatment with the mTORC1 inhibitor rapamycin. These results suggest that primary cilia regulate ventricle morphogenesis by acting as a brake on the mTORC1 pathway. This opens new avenues for the diagnosis and treatment of hydrocephalus. [ABSTRACT FROM AUTHOR]

Published
2017
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37. Genetic tracing of subpopulation neurons in the prethalamus of mice (Mus musculus)

Author

Delauany, Delphine, Heydon, Katharina, Miguez, Andrés, Schwab, Markus, Nave, Klaus-Armin, Thomas, Jean Leon, Spassky, Nathalie, Martínez, Salvador, Zalc, Bernard, Delauany, Delphine, Heydon, Katharina, Miguez, Andrés, Schwab, Markus, Nave, Klaus-Armin, Thomas, Jean Leon, Spassky, Nathalie, Martínez, Salvador, and Zalc, Bernard

Abstract

Genetic labeling based on the Cre/lox reporter system has allowed the creation of fate maps for progenitor cells and their offspring. In the diencephalon, pools of progenitors express the plp transcripts in the zona limitans intrathalamica (ZLI), the basal plate of the diencephalon (bpD), and the posterior part of the hypothalamus. We used plp-Cre transgenics crossed with either Rosa26-lox-lacZ (R26R) or actin-lox gfp (Z/EG) reporter mice to investigate the progeny of plp-expressing ventricular cells in the diencephalon. We describe the subpopulations of prethalamic neurons derived from plp-activated progenitors, their possible migratory routes as development proceeds, and their final positional identity. Neurons derived from plp-expressing progenitors issued from the ZLI contribute to GABAergic cells in the zona incerta, the subgeniculate nucleus, the ventral lateral geniculate, and the intergeniculate leaflet. Plp+ progenitors in the bpD and posterior hypothalamus appear to generate glutamatergic neurons in the subthalamic nucleus and GABAergic neurons in the mammillary and retromammillary tegmentum derivatives. In all these nuclei the contribution of plp+ progenitors is only partial, illustrating the heterogeneity of origin of neurons in prethalamic and caudal hypothalamic nuclei.

Published
2009

39. Oligodendrocyte development in the embryonic brain: The contribution of the plp lineage

Author

Institut National de la Santé et de la Recherche Médicale (France), Ministère de l’Enseignement supérieur et de la Recherche (France), European Commission, Fondation pour l'aide à la recherche sur la sclérose en plaques, Ligue Nationale contre le Cancer (France), Le Bras, Barbara, Chatzopoulou, Elli, Heydon, Katharina, Martínez, Salvador, Ikenaka, Katzuhiko, Prestoz, Laetitia, Spassky, Nathalie, Zalc, Bernard, Thomas, Jean Leon, Institut National de la Santé et de la Recherche Médicale (France), Ministère de l’Enseignement supérieur et de la Recherche (France), European Commission, Fondation pour l'aide à la recherche sur la sclérose en plaques, Ligue Nationale contre le Cancer (France), Le Bras, Barbara, Chatzopoulou, Elli, Heydon, Katharina, Martínez, Salvador, Ikenaka, Katzuhiko, Prestoz, Laetitia, Spassky, Nathalie, Zalc, Bernard, and Thomas, Jean Leon

Abstract

Oligodendrocytes are the myelin forming cells of the central nervous system. Over the last decade, their development in the embryonic brain and spinal cord has been documented following the discovery of early oligodendroglial markers. This review highlights the fundamental results obtained on the specification and migration of oligodendroglial cells and illustrates our advances in the knowledge of the cell lineage expressing plp (proteolipid protein), one of the early oligodendroglial genes.

Published
2005

40. Planar polarity of multiciliated ependymal cells involves the anterior migration of basal bodies regulated by non-muscle myosin II

Author

Hirota, Yuki, primary, Meunier, Alice, additional, Huang, Shihhui, additional, Shimozawa, Togo, additional, Yamada, Osamu, additional, Kida, Yasuyuki S., additional, Inoue, Masashi, additional, Ito, Tsubasa, additional, Kato, Hiroko, additional, Sakaguchi, Masanori, additional, Sunabori, Takehiko, additional, Nakaya, Masa-aki, additional, Nonaka, Shigenori, additional, Ogura, Toshihiko, additional, Higuchi, Hideo, additional, Okano, Hideyuki, additional, Spassky, Nathalie, additional, and Sawamoto, Kazunobu, additional

Published
2010
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41. The ciliary pocket: an endocytic membrane domain at the base of primary and motile cilia

Author

Molla-Herman, Anahi, primary, Ghossoub, Rania, additional, Blisnick, Thierry, additional, Meunier, Alice, additional, Serres, Catherine, additional, Silbermann, Flora, additional, Emmerson, Chris, additional, Romeo, Kelly, additional, Bourdoncle, Pierre, additional, Schmitt, Alain, additional, Saunier, Sophie, additional, Spassky, Nathalie, additional, Bastin, Philippe, additional, and Benmerah, Alexandre, additional

Published
2010
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45. The early steps of oligodendrogenesis: Insights from the study of the plp lineage in the brain of chicks and rodents

Author

Spassky, Nathalie, Olivier, Christelle, Cobos, Inma, Le Bras, Barbara, Goujet-Zalc, Cécile, Martínez, Salvador, Zalc, Bernard, Thomas, Jean Leon, Spassky, Nathalie, Olivier, Christelle, Cobos, Inma, Le Bras, Barbara, Goujet-Zalc, Cécile, Martínez, Salvador, Zalc, Bernard, and Thomas, Jean Leon

Abstract

Oligodendrocytes are the myelin-forming cells of the central nervous system. Over the last decade, their development in the embryonic brain and spinal cord has been documented following the discovery of early oligodendroglial markers. These early expressed oligodendroglial genes nevertheless show differences in their spatiotemporal pattern of expression and it is not yet clear if their expression is linked in a linear way. This review highlights the common themes underlying the spatiotemporal aspects of oligodendrogenesis in chick and rodent brain and discusses some recent advances in the knowledge of the cell lineage expressing plp, one of the early oligodendroglial genes. We suggest a model of oligodendroglial commitment whereby definitive oligodendroglial progenitor formation is preceded by a primitive neuroglial progenitor stage and whereby different oligodendrocyte lineages might segregate from either plp-positive or plp-negative primitive progenitor cells.

Published
2001

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