Roles of organizer factors and BMP antagonism in mammalian forebrain establishment.
Roles of organizer factors and BMP antagonism in mammalian forebrain establishment.
复制标题
组织因子和 BMP 拮抗作用在哺乳动物前脑建立中的作用。
DOI：
10.1016/j.ydbio.2006.06.014
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Klingensmith,John
中科院分区：
文献类型：
--
作者：
Yang,Yu-Ping;Klingensmith,John
哺乳动物发育中的一个关键问题是前脑是如何形成的。在两栖动物中，源自原肠胚组织者的骨形态发生蛋白（BMP）拮抗作用是关键。BMP拮抗剂和组织者在哺乳动物中的作用尚不清楚。前内脏内胚层（AVE）促进小鼠头部的早期发育，但其功能存在争议。在这里，我们探讨了小鼠前脑建立的时间和调节。前脑的特化需要通过原肠胚形成后期的组织相互作用。Foxa 2 −/−胚胎缺乏组织者及其BMP拮抗剂，但约25%的胚胎前脑基因表达较弱。类似的百分比显示异位AVE基因表达远端。因此，远端VE可能是这些胚胎中前脑促进信号的来源。在野生型外胚层外植体，AVE促进前脑规格，而前中内胚层提供维护信号。胚胎学和分子数据表明，AVE是体内活性BMP拮抗作用的来源。在预先指定的外胚层外植体，外源性BMP拮抗剂触发前脑基因表达和抑制后基因表达。相反，BMP抑制前脑基因表达，这种作用可以被前中内胚层拮抗，并促进一些后部基因的表达。这些结果导致一个模型，其中BMP拮抗作用提供的外源性组织促进前脑的建立和维护在小鼠外胚层。
A critical question in mammalian development is how the forebrain is established. In amphibians, bone morphogenetic protein (BMP) antagonism emanating from the gastrula organizer is key. Roles of BMP antagonism and the organizer in mammals remain unclear. Anterior visceral endoderm (AVE) promotes early mouse head development, but its function is controversial. Here, we explore the timing and regulation of forebrain establishment in the mouse. Forebrain specification requires tissue interaction through the late streak stage of gastrulation. Foxa2−/−embryos lack both the organizer and its BMP antagonists, yet about 25% show weak forebrain gene expression. A similar percentage shows ectopic AVE gene expression distally. The distal VE may thus be a source of forebrain promoting signals in these embryos. In wild-type ectoderm explants, AVE promoted forebrain specification, while anterior mesendoderm provided maintenance signals. Embryological and molecular data suggest that the AVE is a source of active BMP antagonism in vivo. In prespecification ectoderm explants, exogenous BMP antagonists triggered forebrain gene expression and inhibited posterior gene expression. Conversely, BMP inhibited forebrain gene expression, an effect that could be antagonized by anterior mesendoderm, and promoted expression of some posterior genes. These results lead to a model in which BMP antagonism supplied by exogenous tissues promotes forebrain establishment and maintenance in the murine ectoderm.