The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo

被引:122
作者
Chen, CH
Ware, SM
Sato, A
Houston-Hawkins, DE
Habas, R
Matzuk, MM
Shen, MM [1 ]
Brown, CW
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, Piscataway, NJ 08854 USA
[3] Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA
[4] Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA
[5] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA
[6] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[7] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA
[8] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
来源
DEVELOPMENT | 2006年 / 133卷 / 02期
关键词
Tg beta signaling; EGF-CFC proteins; anterior visceral endoderm; mesendoderm formation;
D O I
10.1242/dev.02210
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:319 / 329
页数:11
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