MTORC1 signaling and primary cilia are required for brain ventricle morphogenesis

P Foerster, M Daclin, S Asm, M Faucourt, A Boletta, A Genovesio, N Spassky

Research output: Contribution to journalArticle

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. © 2017. Published by The Company of Biologists Ltd.
Original languageEnglish
Pages (from-to)201-210
Number of pages10
JournalDevelopment (Cambridge)
Volume144
Issue number2
DOIs
Publication statusPublished - 2017

Fingerprint

Cilia
Morphogenesis
Neuroglia
Brain
Hydrocephalus
Ependymoglial Cells
Cerebral Ventricles
Spindle Apparatus
Neurogenesis
Sirolimus
Embryonic Development
Dilatation
Stem Cells
Phenotype
Neurons
mechanistic target of rapamycin complex 1

Cite this

Foerster, P., Daclin, M., Asm, S., Faucourt, M., Boletta, A., Genovesio, A., & Spassky, N. (2017). MTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development (Cambridge), 144(2), 201-210. https://doi.org/10.1242/dev.138271

MTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. / Foerster, P; Daclin, M; Asm, S; Faucourt, M; Boletta, A; Genovesio, A; Spassky, N.

In: Development (Cambridge), Vol. 144, No. 2, 2017, p. 201-210.

Research output: Contribution to journalArticle

Foerster, P, Daclin, M, Asm, S, Faucourt, M, Boletta, A, Genovesio, A & Spassky, N 2017, 'MTORC1 signaling and primary cilia are required for brain ventricle morphogenesis', Development (Cambridge), vol. 144, no. 2, pp. 201-210. https://doi.org/10.1242/dev.138271
Foerster, P ; Daclin, M ; Asm, S ; Faucourt, M ; Boletta, A ; Genovesio, A ; Spassky, N. / MTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. In: Development (Cambridge). 2017 ; Vol. 144, No. 2. pp. 201-210.
@article{46dff401b7574973a19bee25f15f27fd,
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. {\circledC} 2017. Published by The Company of Biologists Ltd.",
author = "P Foerster and M Daclin and S Asm and M Faucourt and A Boletta and A Genovesio and N Spassky",
year = "2017",
doi = "10.1242/dev.138271",
language = "English",
volume = "144",
pages = "201--210",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "2",

}

TY - JOUR

T1 - MTORC1 signaling and primary cilia are required for brain ventricle morphogenesis

AU - Foerster, P

AU - Daclin, M

AU - Asm, S

AU - Faucourt, M

AU - Boletta, A

AU - Genovesio, A

AU - Spassky, N

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. © 2017. Published by The Company of Biologists Ltd.

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. © 2017. Published by The Company of Biologists Ltd.

U2 - 10.1242/dev.138271

DO - 10.1242/dev.138271

M3 - Article

VL - 144

SP - 201

EP - 210

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 2

ER -