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Maternal Gdf3 is an obligatory cofactor in nodal signaling for embryonic axis formation in zebrafish
eLife ( IF 6.4 ) Pub Date : 2017-11-15 , DOI: 10.7554/elife.28534
Brent W Bisgrove 1 , Yi-Chu Su 1 , H Joseph Yost 1
Affiliation  

Zebrafish Gdf3 (Dvr1) is a member of the TGFβ 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 TGFβ 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.

中文翻译:

母体 Gdf3 是斑马鱼胚胎轴形成的节点信号传导的必需辅因子

斑马鱼 Gdf3 (Dvr1) 是 TGFβ 细胞信号配体超家族的成员,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 导致胚胎致死率,可以用 gdf3 RNA 完全挽救,这表明 Gdf3 仅在发育早期才需要,超过此突变体是可行和可育的。Gdf3 突变体对 Nodal 配体和 Nodal 阻遏物 Lefty1 具有耐药性。由 TGFβ 配体激活素和组成型活性受体 Alk4 和 Alk2 驱动的信号传导在 gdf3 突变体中保持完整,表明 Gdf3 在与 Nodal 相同的通路步骤中发挥作用。将 gdf3 和 ndr2 RNA 靶向特定谱系表明外源 gdf3 只有在与内源性 Nodal 共表达时才能完全拯救突变体。总之,这些发现表明 Gdf3 是胚胎轴建立过程中节点信号传导的重要辅助因子。
更新日期:2017-11-15
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