VegT activation of Sox17 at the midblastula transition alters the response to nodal signals in the vegetal endoderm domain
VegT activation of Sox17 at the midblastula transition alters the response to nodal signals in the vegetal endoderm domain
复制标题
DOI：
10.1006/dbio.2001.0366
复制
发表时间：
2001-09-01
影响因子：
2.7
通讯作者：
Kessler, DS
中科院分区：
文献类型：
--
作者：
Engleka, MJ;Craig, EJ;Kessler, DS
在Xenopas中，预期的内胚层和中胚层在原肠胚形成开始时定位于离散的相邻区域，并且这通过Sox 17在植物性卵裂球中的表达和Brachyury（Xbra）在边缘卵裂球中的表达而变得明显。在这里，我们研究了Sox 17 α表达的调节和Sox 17 α在建立植物内胚层基因表达域中的作用。注射VegT或Nodal的特异性抑制剂导致原肠胚中Sox 17 α表达的丧失。然而，Sox 17 α在中胚转变时表达的开始依赖于VegT，而不是Nodal功能，表明Sox 17 α表达由VegT启动，然后由Nodal信号维持。与这些结果一致，VegT，而不是爪蟾结节相关的-1（Xnr 1），可以激活Sox 17 α在动物外植体中囊胚阶段的表达。此外，VegT在放线菌酮或Nodal拮抗剂存在下激活Sox 17 α，表明Sox 17 α是VegT在植物性卵裂球中的立即早期靶点。考虑到Nodal信号对于中胚层和内胚层基因表达是必要和充分的，我们建议在中胚转变时Sox 17 α的VegT激活阻止中胚层基因表达响应于Nodal信号，从而建立植物内胚层基因表达域。支持这一观点，Sox 17 α在边缘区的错误表达抑制了多个中胚层基因的表达。此外，在动物外植体中，Sox 17 alpha阻止Xbra和MyoD的诱导，但不阻止Sox 17 beta或Mixer对Xnr 1的反应。因此，Sox 17 α的VegT激活在植物卵裂球中建立内胚层特异性基因表达区域中起重要作用。(C)北京：科学出版社.
In Xenopas, the prospective endoderm and mesoderm are localized to discrete, adjacent domains at the beginning of gastrulation, and this is made evident by the expression of Sox17 in vegetal blastomeres and Brachyury (Xbra) in marginal blastomeres. Here, we examine the regulation of Sox17 alpha expression and the role of Sox17 alpha in establishing the vegetal endodermal gene expression domain. Injection of specific inhibitors of VegT or Nodal resulted in a loss of Sox17 alpha expression in the gastrula. However, the onset of Sox17 alpha expression at the midblastula transition was dependent on VegT, but not on Nodal function, indicating that Sox17 alpha expression is initiated by VegT and then maintained by Nodal signals. Consistent with these results, VegT, but not Xenopus Nodal-related-1 (Xnr1), can activate Sox17 alpha expression at the midblastula stage in animal explants. In addition, VegT activates Sox17 alpha in the presence of cycloheximide or a Nodal antagonist, suggesting that Sox17 alpha is an immediate-early target of VegT in vegetal blastomeres. Given that Nodal signals are necessary and sufficient for both mesodermal and endodermal gene expression, we propose that VegT activation of Sox17 alpha at the midblastula transition prevents mesodermal gene expression in response to Nodal signals, thus establishing the vegetal endodermal gene expression domain. Supporting this idea, Sox17 alpha misexpression in the marginal zone inhibits the expression of multiple mesodermal genes. Furthermore, in animal explants, Sox17 alpha prevents the induction of Xbra and MyoD, but not Sox17 beta or Mixer, in response to Xnr1. Therefore, VegT activation of Sox17 alpha plays an important role in establishing a region of endoderm-specific gene expression in vegetal blastomeres. (C) 2001 Academic Press.