Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without maternally provided vg1 fail to form endoderm and head and trunk mesoderm, and closely resemble nodal loss-of-function mutants. Although Nodal is processed and secreted without Vg1, it requires Vg1 for its endogenous activity. Conversely, Vg1 is unprocessed and resides in the endoplasmic reticulum without Nodal, and is only secreted, processed and active in the presence of Nodal. Co-expression of Nodal and Vg1 results in heterodimer formation and mesendoderm induction. Thus, mesendoderm induction relies on the combination of two TGF-beta-related signals: maternal and ubiquitous Vg1, and zygotic and localized Nodal. Modeling reveals that the pool of maternal Vg1 enables rapid signaling at low concentrations of zygotic Nodal.

Nodal被认为是脊椎动物胚胎和胚胎干细胞中内胚层的关键诱导剂。其他TGF-beta相关信号，例如Vg1 / Dvr1 / Gdf3，也参与了这一过程，但其作用尚不清楚或存在争议。在这里，我们报告没有母体提供的vg1的斑马鱼胚胎无法形成内胚层，头和躯干中胚层，并且与结节非常相似功能丧失的突变体。尽管Nodal是在没有Vg1的情况下进行加工和分泌的，但其内源活性仍需要Vg1。相反，Vg1是未经加工的，位于没有Nodal的内质网中，仅在存在Nodal的情况下才分泌，加工并具有活性。Nodal和Vg1的共表达导致异二聚体的形成和中胚层的诱导。因此，中胚层诱导依赖于两种TGF-β相关信号的组合：母体和普遍存在的Vg1，以及合子和局部Nodal。建模显示，母体Vg1库可在低浓度的合子Nodal时实现快速信号传递。