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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Polycomb 组蛋白 Ring1 调节小鼠端脑的背腹侧模式

DOI:
10.1101/639492
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发表时间:
2019
期刊:
bioRxiv
影响因子:
--
通讯作者:
Gotoh Yukiko
Gotoh Yukiko
中科院分区:
--
文献类型:
--
作者:
Eto Hikaru;Kishi Yusuke;Koseki Haruhiko;Gotoh Yukiko

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哺乳动物端脑的背-腹模式对于包括新皮层和神经节隆起在内的不同功能区域的形成至关重要。虽然骨形态发生蛋白(BMP),Wnt和Sonic hedgehog(Shh)信号传导已知决定区域身份沿着背腹轴,如何建立这些形态发生蛋白的区域特异性表达仍不清楚。在这里,我们表明,Polycomb组(PcG)蛋白Ring 1有助于小鼠端脑的腹侧化。Ring 1bor Ring 1a和Ring 1bin神经上皮细胞的缺失诱导背侧基因的异位表达,包括BMP和Wnt配体的异位表达,以及腹侧端脑Shh基因的减弱表达,Shh是腹侧化的关键形态原。我们观察到PcG蛋白介导的组蛋白3在赖氨酸-27处的三甲基化和Ring 1B在BMP和Wnt配体基因特异性地在腹侧区域的结合。此外,BMP或Wnt信号的强制激活抑制Shh表达。因此,我们的研究结果表明,PcG蛋白抑制BMP和Wnt信号在特定区域的方式,从而允许适当的Shh表达和腹侧端脑的发展。
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 ofRing1bor bothRing1aandRing1bin 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.
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