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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mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. / Foerster, Philippe; Daclin, Marie; Shihavuddin, Asm; Faucourt, Marion; Boletta, Alessandra; Genovesio, Auguste; Spassky, Nathalie.

In: Journal of Cell Science, Vol. 130, No. 3, 2017, p. 201-210.

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

Harvard

Foerster, P, Daclin, M, Shihavuddin, A, Faucourt, M, Boletta, A, Genovesio, A & Spassky, N 2017, 'mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis', Journal of Cell Science, vol. 130, no. 3, pp. 201-210. https://doi.org/10.1242/dev.138271

APA

Foerster, P., Daclin, M., Shihavuddin, A., Faucourt, M., Boletta, A., Genovesio, A., & Spassky, N. (2017). mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Journal of Cell Science, 130(3), 201-210. https://doi.org/10.1242/dev.138271

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MLA

Vancouver

Author

Foerster, Philippe ; Daclin, Marie ; Shihavuddin, Asm ; Faucourt, Marion ; Boletta, Alessandra ; Genovesio, Auguste ; Spassky, Nathalie. / mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. In: Journal of Cell Science. 2017 ; Vol. 130, No. 3. pp. 201-210.

Bibtex

@article{b00ef3cfd2f54f578d84ca9ff1cded70,
title = "mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis",
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.",
keywords = "Cilia, Hydrocephalus, MTORC1 pathway, Ventricular system",
author = "Philippe Foerster and Marie Daclin and Asm Shihavuddin and Marion Faucourt and Alessandra Boletta and Auguste Genovesio and Nathalie Spassky",
year = "2017",
doi = "10.1242/dev.138271",
language = "English",
volume = "130",
pages = "201--210",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "The/Company of Biologists Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis

AU - Foerster, Philippe

AU - Daclin, Marie

AU - Shihavuddin, Asm

AU - Faucourt, Marion

AU - Boletta, Alessandra

AU - Genovesio, Auguste

AU - Spassky, Nathalie

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Cilia

KW - Hydrocephalus

KW - MTORC1 pathway

KW - Ventricular system

U2 - 10.1242/dev.138271

DO - 10.1242/dev.138271

M3 - Journal article

VL - 130

SP - 201

EP - 210

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 3

ER -