Journal article
mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis
Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM U1024, and CNRS UMR 8197, PSL Research University, 46 rue d'Ulm, Paris 75005, France.
Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan 20132, Italy.
Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM U1024, and CNRS UMR 8197, PSL Research University, 46 rue d'Ulm, Paris 75005, France nathalie.spassky@ens.fr.
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.
Language: | Undetermined |
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Publisher: | The Company of Biologists Ltd |
Year: | 2017 |
Pages: | 201-210 |
ISSN: | 14779129 and 09501991 |
Types: | Journal article |
DOI: | 10.1242/dev.138271 |
ORCIDs: | Spassky, Nathalie |
Animals Brain Cell Polarity Cerebral Ventricles Cilia Embryo, Mammalian Female Hydrocephalus Mechanistic Target of Rapamycin Complex 1 Mice Mice, Inbred C57BL Mice, Transgenic Morphogenesis Multiprotein Complexes Neurogenesis Neurons Pregnancy Signal Transduction Sirolimus TOR Serine-Threonine Kinases Ventricular system mTOR protein, mouse mTORC1 pathway