Notch and Hippo signaling converge on Strawberry Notch 1 (Sbno1) to synergistically activate Cdx2 during specification of the trophectoderm.
Notch and Hippo signaling converge on Strawberry Notch 1 (Sbno1) to synergistically activate Cdx2 during specification of the trophectoderm.
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DOI：
10.1038/srep46135
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发表时间：
2017-04-12
影响因子：
4.6
通讯作者：
Ogura T
中科院分区：
文献类型：
--
作者：
Watanabe Y;Miyasaka KY;Kubo A;Kida YS;Nakagawa O;Hirate Y;Sasaki H;Ogura T
第一个二元细胞命运决定发生在桑椹胚阶段，并产生两种不同类型的细胞，构成滋养外胚层（TE）和内细胞团（ICM）。细胞命运决定因子Cdx 2在TE细胞中被诱导，并在其分化和维持中起重要作用。Notch和Hippo信号级联被认为会聚到Cdx 2的调节元件上，然而，基本的分子机制在很大程度上是未知的。在这里，我们表明参与草莓Notch 1（Sbno 1），一种新的染色质因子的解旋酶超家族2，在植入前的发展。Sbno 1基因敲除的胚胎在植入前阶段死亡，没有形成囊胚腔，Cdx 2没有打开，即使雅普和Tead 4都正常存在于细胞核中。因此，Sbno 1作用于Cdx 2的滋养外胚层增强子（TEE），确保其通过雅普/Tead 4和NICD/Rbpj复合物的稳健和协同激活。有趣的是，当细胞被机械拉伸时，这种协同作用增强，这可能反映了TE细胞被扩张的ICM和囊胚腔持续拉伸。此外，组蛋白伴侣，FACT（FACilitates染色质转录）与Sbno 1物理相互作用。我们的数据提供了新的证据TE规格，突出了意想不到的，但重要的功能，高度保守的染色质因子，Sbno 1。
The first binary cell fate decision occurs at the morula stage and gives rise to two distinct types of cells that constitute the trophectoderm (TE) and inner cell mass (ICM). The cell fate determinant, Cdx2, is induced in TE cells and plays an essential role in their differentiation and maintenance. Notch and Hippo signaling cascades are assumed to converge onto regulatory elements of Cdx2, however, the underlying molecular mechanisms are largely unknown. Here, we show involvement of Strawberry Notch1 (Sbno1), a novel chromatin factor of the helicase superfamily 2, during preimplantation development. Sbno1 knockout embryos die at the preimplantation stage without forming a blastocoel, and Cdx2 is not turned on even though both Yap and Tead4 reside normally in nuclei. Accordingly, Sbno1 acts on the trophectoderm-enhancer (TEE) of Cdx2, ensuring its robust and synergistic activation by the Yap/Tead4 and NICD/Rbpj complexes. Interestingly, this synergism is enhanced when cells are mechanically stretched, which might reflect that TE cells are continuously stretched by the expanding ICM and blastocoel cavity. In addition, the histone chaperone, FACT (FAcilitates Chromatin Transcription) physically interacts with Sbno1. Our data provide new evidence on TE specification, highlighting unexpected but essential functions of the highly conserved chromatin factor, Sbno1.