Zebrafish Gdf3 (Dvr1) is a member of the TGFb superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3. Surprisingly, engineered homozygous mutants in zebrafish have no apparent phenotype. Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can be fully rescued with gdf3 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. Gdf3 mutants are refractory to Nodal ligands and Nodal repressor Lefty1. Signaling driven by TGFb ligand Activin and constitutively active receptors Alk4 and Alk2 remain intact in gdf3 mutants, indicating that Gdf3 functions at the same pathway step as Nodal. Targeting gdf3 and ndr2 RNA to specific lineages indicates that exogenous gdf3 is able to fully rescue mutants only when co-expressed with endogenous Nodal. Together, these findings demonstrate that Gdf3 is an essential cofactor of Nodal signaling during establishment of the embryonic axis.

斑马鱼Gdf3（Dvr1）是TGFb细胞信号配体超家族的成员，该配体包括非洲爪蟾Vg1和哺乳动物Gdf1 / 3。令人惊讶的是，斑马鱼中的工程纯合突变体没有明显的表型。消除母体-合子突变体卵母细胞中的Gdf3可以使胚胎致死，可以用gdf3 RNA完全挽救它的生命力，这表明Gdf3仅在发育早期才需要，在此之后突变体才是可行且可育的。Gdf3突变体是难治性的节点配体和节点阻遏物Lefty1。由TGFb配体激活素和组成性活性受体Alk4和Alk2驱动的信号在gdf3突变体中保持完整，表明Gdf3在与Nodal相同的途径步骤中起作用。定位到gdf3和NDR2 RNA特定谱系表明，外源GDF3能够完全救援的突变体与内源性交点只有当共表达。总之，这些发现表明，Gdf3是建立胚胎轴期间Nodal信号传导的重要辅助因子。