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Dev Cell. 2011 Jan 18;20(1):97-108. doi: 10.1016/j.devcel.2010.11.020.

Rheb1 is required for mTORC1 and myelination in postnatal brain development.

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1
The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.

Abstract

mTor kinase is involved in cell growth, proliferation, and differentiation. The roles of mTor activators, Rheb1 and Rheb2, have not been established in vivo. Here, we report that Rheb1, but not Rheb2, is critical for embryonic survival and mTORC1 signaling. Embryonic deletion of Rheb1 in neural progenitor cells abolishes mTORC1 signaling in developing brain and increases mTORC2 signaling. Remarkably, embryonic and early postnatal brain development appears grossly normal in these Rheb1f/f,Nes-cre mice with the notable exception of deficits of myelination. Conditional expression of Rheb1 transgene in neural progenitors increases mTORC1 activity and promotes myelination in the brain. In addition the Rheb1 transgene rescues mTORC1 signaling and hypomyelination in the Rheb1f/f,Nes-cre mice. Our study demonstrates that Rheb1 is essential for mTORC1 signaling and myelination in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability.

PMID:
21238928
PMCID:
PMC3056331
DOI:
10.1016/j.devcel.2010.11.020
[Indexed for MEDLINE]
Free PMC Article

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