Molecular Medicine Program, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, United States.
Elife. 2017 Nov 15;6:e28534. doi: 10.7554/eLife.28534.
Zebrafish Gdf3 (Dvr1) is a member of the TGFβ superfamily of cell signaling ligands that includes 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 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. mutants are refractory to Nodal ligands and Nodal repressor Lefty1. Signaling driven by TGFβ ligand Activin and constitutively active receptors Alk4 and Alk2 remain intact in mutants, indicating that Gdf3 functions at the same pathway step as Nodal. Targeting and RNA to specific lineages indicates that exogenous 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 TGFβ 细胞信号配体超家族的成员之一，该超家族还包括 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。在母-合子突变体的卵母细胞中消除 Gdf3 会导致胚胎致死，而用 RNA 完全挽救这一结果，表明 Gdf3 仅在早期发育中是必需的，在此之后突变体是存活且可育的。突变体对 Nodal 配体和 Nodal 抑制剂 Lefty1 具有抗性。在 突变体中，TGFβ 配体 Activin 驱动的信号传导以及组成性激活的受体 Alk4 和 Alk2 仍然完整，表明 Gdf3 在与 Nodal 相同的途径步骤中发挥作用。将 和 RNA 靶向特定谱系表明，外源性 只有在与内源性 Nodal 共同表达时才能完全挽救突变体。这些发现表明，Gdf3 在胚胎轴的建立过程中是 Nodal 信号的必需共因子。
