LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain.
LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain.
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LSD1 共阻遏物 Rcor2 协调小鼠大脑发育中的神经发生
DOI：
10.1038/ncomms10481
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发表时间：
2016-01-22
影响因子：
16.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wang Y;Wu Q;Yang P;Wang C;Liu J;Ding W;Liu W;Bai Y;Yang Y;Wang H;Gao S;Wang X
表观遗传调控复合物在调节神经干细胞（NSC）增殖和后代特化的转录调控中起关键作用。特定的辅因子如何引导组蛋白去甲基化酶LSD 1/KDM 1A复合物调节皮层神经发生中不同的NSCs相关基因激活和抑制仍不清楚。在这里，我们证明，Rcor 2，LSD 1的辅阻遏物，主要在中枢神经系统（CNS）中表达，并在皮质发育的表观遗传调控中起着关键作用。Rcor 2的消耗导致NPC增殖、神经元群体、新皮质厚度和脑大小减少。我们发现Rcor 2直接靶向Dlx 2和Shh，并抑制它们在发育中的新皮层中的表达。此外，Shh信号的抑制挽救了体内和体外由Rcor 2缺失引起的神经发生缺陷。因此，我们的研究结果表明，辅阻遏蛋白Rcor 2是至关重要的皮质发育，通过抑制Shh信号通路在背侧端脑。
Epigenetic regulatory complexes play key roles in the modulation of transcriptional regulation underlying neural stem cell (NSC) proliferation and progeny specification. How specific cofactors guide histone demethylase LSD1/KDM1A complex to regulate distinct NSC-related gene activation and repression in cortical neurogenesis remains unclear. Here we demonstrate that Rcor2, a co-repressor of LSD1, is mainly expressed in the central nervous system (CNS) and plays a key role in epigenetic regulation of cortical development. Depletion of Rcor2 results in reduced NPC proliferation, neuron population, neocortex thickness and brain size. We find that Rcor2 directly targets Dlx2 and Shh, and represses their expressions in developing neocortex. In addition, inhibition of Shh signals rescues the neurogenesis defects caused by Rcor2 depletion bothin vivoandin vitro. Hence, our findings suggest that co-repressor Rcor2 is critical for cortical development by repressing Shh signalling pathway in dorsal telencephalon.