Journal
DEVELOPMENT
Volume 144, Issue 2, Pages 201-210Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.138271
Keywords
Cilia; Ventricular system; mTORC1 pathway; Hydrocephalus
Categories
Funding
- French National Research Agency [ANR-10-INBS- 04, ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL]
- Region Ile-de-France (NERF) [2011-45]
- Fondation pour la Recherche Medicale [DGE 20111123023, FRM20140329547]
- Federation pour la Recherche sur le Cerveau - Rotary International France
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Centre National de la Recherche Scientifique (CNRS)
- Ecole Normale Superieure (ENS)
- ANR [ANR-12-BSV4-0006]
- European Research Council [647466]
- Canceropole-IDF [2014-1-PL BIO-11-INSERM 12-1]
- Fondation Pierre-Gilles de Gennes [FPGG03]
- program Investissements d'Avenir' of the French Government by the ANR [ANR-11-IDEX-0001-02 PSL, ANR-10-LABX-54 MEMOLIFE]
- Sorbonne Universites
- MEMO LIFE program
- European Research Council (ERC) [647466] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-12-BSV4-0006] Funding Source: Agence Nationale de la Recherche (ANR)
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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.
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