【原】Rheb1是mTORC1和出生后脑发育中髓鞘形成所必需的

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

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|核心内容：

MTOR激酶参与细胞的生长、增殖和分化。

MTOR激活剂Rheb1和Rheb2在体内的作用尚未确定。

在这里，我们报告Rheb1，而不是Rheb2，对胚胎存活和mTORC1信号是关键的。

胚胎缺失神经前体细胞中的Rheb1可以丢失发育脑中的mTORC1信号，并增加mTORC2信号。

值得注意的是，在这些Rheb1f/f，nes-cre小鼠中，胚胎和出生后早期的大脑发育总体上是正常的，但髓鞘形成障碍是一个显著的例外。

Rheb1转基因在神经前体细胞中的条件性表达增加了mTORC1的活性，并促进了大脑中的髓鞘形成。

此外，Rheb1转基因可以挽救Rheb1f/f，Nes-cre小鼠的mTORC1信号和髓鞘过少。

我们的研究表明，Rheb1对mTORC1信号和脑内髓鞘形成是必不可少的，并提示mTORC1信号在选择性细胞适应中发挥作用，而不是在一般细胞存活中起作用。

原文摘要：

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.

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参考文献：https:///10.1016/j.devcel.2010.11.020

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