The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon.

The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon.
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DOI:
10.1038/s41467-020-19556-5
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发表时间:
2020-11-11
影响因子:
16.6
通讯作者:
Gotoh Y
Gotoh Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Eto H;Kishi Y;Yakushiji-Kaminatsui N;Sugishita H;Utsunomiya S;Koseki H;Gotoh Y

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哺乳动物端脑的背腹模式是形成包括新皮质和神经节隆起在内的不同功能区域的基础。虽然已知骨形态发生蛋白(BMP)、Wnt和Sonic hedgehog(Shh)信号决定了背腹轴的区域同一性,但这些形态原的区域特异性表达如何仍不清楚。在这里,我们证明了聚梳组(PcG)蛋白Ring1对小鼠端脑的腹腔化起作用。神经上皮细胞中Ring1b或Ring1a和Ring1b的缺失导致背侧基因的异位表达,包括BMP和Wnt配体的基因表达,以及腹侧端脑的关键形态形成物Shh的基因表达减弱。我们观察到PcG蛋白介导的组蛋白3在赖氨酸-27处的三甲基化,以及Ring1b在BMP和Wnt配体基因上的结合,特别是在腹侧区域。此外,BMP或Wnt信号的强制激活抑制了Shh的表达。因此,我们的结果表明,PcG蛋白以区域特异性的方式抑制BMP和Wnt信号,从而允许适当的Shh表达和腹侧端脑的发育。NCOMMS-19-38235B哺乳动物端脑的背腹模式是形成不同功能区的基础。在这里,作者发现PcG蛋白以区域特异性的方式抑制BMP和Wnt信号,允许适当的Shh表达和腹侧端脑的发育。
Dorsal-ventral patterning of the mammalian telencephalon is fundamental to the formation of distinct functional regions including the neocortex and ganglionic eminence. While Bone morphogenetic protein (BMP), Wnt, and Sonic hedgehog (Shh) signaling are known to determine regional identity along the dorsoventral axis, how the region-specific expression of these morphogens is established remains unclear. Here we show that the Polycomb group (PcG) protein Ring1 contributes to the ventralization of the mouse telencephalon. Deletion of Ring1b or both Ring1a and Ring1b in neuroepithelial cells induces ectopic expression of dorsal genes, including those for BMP and Wnt ligands, as well as attenuated expression of the gene for Shh, a key morphogen for ventralization, in the ventral telencephalon. We observe PcG protein–mediated trimethylation of histone 3 at lysine-27 and binding of Ring1B at BMP and Wnt ligand genes specifically in the ventral region. Furthermore, forced activation of BMP or Wnt signaling represses Shh expression. Our results thus indicate that PcG proteins suppress BMP and Wnt signaling in a region-specific manner and thereby allow proper Shh expression and development of the ventral telencephalon. NCOMMS-19-38235B Dorsal-ventral patterning of the mammalian telencephalon is fundamental to the formation of distinct functional regions. Here, the authors find that PcG proteins suppress BMP and Wnt signaling in a region-specific manner, allowing for proper Shh expression and development of the ventral telencephalon.
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