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Inactivation of mTORC1 in the developing brain causes microcephaly and affects gliogenesis

Cloëtta, Dimitri and Thomanetz, Venus and Baranek, Constanze and Lustenberger, Regula M. and Lin, Shuo and Oliveri, Filippo and Atanasoski, Suzana and Rüegg, Markus A.. (2013) Inactivation of mTORC1 in the developing brain causes microcephaly and affects gliogenesis. The Journal of Neuroscience, 33 (18). pp. 7799-7810.

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Abstract

The mammalian target of rapamycin (mTOR) regulates cell growth in response to various intracellular and extracellular signals. It assembles into two multiprotein complexes: the rapamycin-sensitive mTOR complex 1 (mTORC1) and the rapamycin-insensitive mTORC2. In this study, we inactivated mTORC1 in mice by deleting the gene encoding raptor in the progenitors of the developing CNS. Mice are born but never feed and die within a few hours. The brains deficient for raptor show a microcephaly starting at E17.5 that is the consequence of a reduced cell number and cell size. Changes in cell cycle length during late cortical development and increased cell death both contribute to the reduction in cell number. Neurospheres derived from raptor-deficient brains are smaller, and differentiation of neural progenitors into glia but not into neurons is inhibited. The differentiation defect is paralleled by decreased Stat3 signaling, which is a target of mTORC1 and has been implicated in gliogenesis. Together, our results show that postnatal survival, overall brain growth, and specific aspects of brain development critically depend on mTORC1 function.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Cellular Neurobiology (Atanasoski)
UniBasel Contributors:Atanasoski, Suzana
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Society for Neuroscience
ISSN:0270-6474
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:10 Feb 2020 14:00
Deposited On:10 Feb 2020 13:21

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