The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo
The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo
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DOI：
10.1242/dev.02210
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发表时间：
2006-01-01
期刊：
影响因子：
4.6
通讯作者：
Brown, CW
中科院分区：
文献类型：
--
作者：
Chen, CH;Ware, SM;Brown, CW
前内脏内胚层（AVE）在原肠胚形成前的小鼠胚胎中的形成代表了前-后轴模式的关键事件。在这里，我们表明，转化生长因子β（TGF β）家族成员Gdf 3（生长分化因子3），非洲爪蟾Vg 1的近亲，类似于TGF β配体Nodal在其信号传导活性和其在体内AVE形成的作用。因此，在细胞培养中，Gdf 3信号传导需要EGF-CFC共受体Cripto，并且可以被Lefty拮抗剂抑制。在非洲爪蟾胚胎中，Gdf 3的错误表达导致第二轴的形成，并诱导动物帽的形态发生伸长和中内胚层的形成。在小鼠胚胎中，Gdf 3在内细胞团和外胚层中表达，并且无效突变体经常表现出AVE的异常形成或定位。这种表型与中胚层和定形内胚层形成的缺陷以及异常的Nodal表达水平相关。我们的研究结果表明，Gdf 3在原肠胚形成前的发展中的Nodal样信号通路中起作用，并为小鼠Vg 1活性的功能保护提供证据。
The formation of the anterior visceral endoderm (AVE) in the pre-gastrulation mouse embryo represents a crucial event in patterning of the anterior-posterior axis. Here, we show that the transforming growth factor beta (Tgf beta) family member Gdf3 (growth-differentiation factor 3), a close relative of Xenopus Vg1, resembles the Tgf beta ligand Nodal in both its signaling activity and its role in AVE formation in vivo. Thus, in cell culture, Gdf3 signaling requires the EGF-CFC co-receptor Cripto and can be inhibited by Lefty antagonists. In Xenopus embryos, Gdf3 misexpression results in secondary axis formation, and induces morphogenetic elongation and mesendoderm formation in animal caps. In mouse embryos, Gdf3 is expressed in the inner cell mass and epiblast, and null mutants frequently exhibit abnormal formation or positioning of the AVE. This phenotype correlates with defects in mesoderm and definitive endoderm formation, as well as abnormal Nodal expression levels. Our findings indicate that Gdf3 acts in a Nodal-like signaling pathway in pre-gastrulation development, and provide evidence for the functional conservation of Vg1 activity in mice.