mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis

Research output: Contribution to journalJournal article – Annual report year: 2017Researchpeer-review

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  • Author: Foerster, Philippe

    PSL Research University

  • Author: Daclin, Marie

    PSL Research University

  • Author: Shihavuddin, Asm

    PSL Research University

  • Author: Faucourt, Marion

    PSL Research University

  • Author: Boletta, Alessandra

    Vita-Salute San Raffaele University

  • Author: Genovesio, Auguste

    PSL Research University

  • Author: Spassky, Nathalie

    PSL Research University

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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.

Original languageEnglish
JournalJournal of Cell Science
Issue number3
Pages (from-to)201-210
Number of pages10
Publication statusPublished - 2017
Externally publishedYes
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • Cilia, Hydrocephalus, MTORC1 pathway, Ventricular system

ID: 140380657