日前，由四川大學(xué)生物治療國家重點(diǎn)實(shí)驗(yàn)室/華西醫(yī)院神經(jīng)分子生物學(xué)實(shí)驗(yàn)室肖波教授帶領(lǐng)的研究小組完成了題為“Rheb1 Is Required for mTORC1 and Myelination in Postnatal Brain Development”的學(xué)術(shù)論文,。該論文發(fā)表在今年1月20日的 Developmental Cell 雜志上（Cell子刊系列雜志,，5年平均IF為14.058）。
由一類名為少突膠質(zhì)細(xì)胞的神經(jīng)細(xì)胞形成的髓鞘對于人類大腦的信息處理過程非常重要,，然而,，少突膠質(zhì)細(xì)胞的發(fā)育以及它們包裹軸突形成髓鞘的分子機(jī)制仍然是不清楚的。肖波教授帶領(lǐng)幾位研究生鄒嘉,、周亮（共同第一作者,，2006級(jí)）等開展了大量的研究工作，發(fā)現(xiàn)Rheb/mTor信號(hào)在該過程中起著很重要的作用。由于mTor 信號(hào)在發(fā)育生物學(xué),、腫瘤研究,、免疫學(xué)以及神經(jīng)精神疾病的調(diào)控中的都具有重要作用，因此mTor相關(guān)研究也是生物醫(yī)學(xué)競爭最為激烈的領(lǐng)域之一,。正如評(píng)審人所說,，“該研究采用了一系列強(qiáng)有力的研究手段如遺傳修飾小鼠、生物化學(xué)以及細(xì)胞成像等來揭示生物醫(yī)學(xué)研究中的一個(gè)重要科學(xué)問題,，該研究詳細(xì)充分地分析了Rheb/mTor信號(hào)在出生后腦發(fā)育,、尤其是髓鞘形成中的作用。”該文的第一作者鄒嘉表示：“在已發(fā)表的文章中,，僅在一篇文章中就采用如此多種敲除敲入小鼠模型開展研究這在國內(nèi)是極少見的,。”肖波教授也指出：“mTor信號(hào)對髓鞘的調(diào)控作用存在爭議，我們的工作首次證明了Rheb/mTor信號(hào)對髓鞘發(fā)育具有促進(jìn)作用,。”（生物谷Bioon.com）
生物谷推薦原文出處：
Developmental Cell doi:10.1016/j.devcel.2010.11.020
Rheb1 Is Required for mTORC1 and Myelination in Postnatal Brain Development
Jia Zou, Liang Zhou, Xiao-Xia Du, Yifei Ji, Jia Xu, Junlong Tian, Wanxiang Jiang, Yi Zou, Shouyang Yu, Lingxue Gan, Maowen Luo, Qiaona Yang, Yiyuan Cui, Wanchun Yang, Xiaoqiang Xia, Mina Chen, Xia Zhao, Ying Shen, Po Yu Chen, Paul F. Worley, Bo Xiao
Highlights
Rheb1, but not Rheb2, is essential for mTORC1 signaling
Rheb1 and Rheb2 are not essential for mTORC2 signaling
Rheb/mTORC1 signaling is a positive regulator of postnatal myelination in the brain
Summary
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.
