Regulation of Cell Fate by Processed Vg1 Protein

Abstract

Mesoderm induction during Xenopus development has been extensively studied, and two members of the transforming growth factor-β family, activin βB and Vg1, have emerged as strong candidates for the natural inducer of dorsal mesoderm. Analysis of Vg1 activity has relied on injection of hybrid Vg1 molecules, which have not been shown to direct efficient secretion of active ligand and therefore, the mechanism of mesoderm induction by processed Vg1 is unclear. Injection of Xenopus oocytes with a chimeric activin-Vg1 mRNA, encoding the pro-region of activin βB fused to the mature region of Vg1, directed the processing and secretion of mature Vg1, resulting in soluble preparations with a concentration of 100–500 ng/ml. Treatment of animal pole expiants with mature Vg1 resulted in formation of dorsal mesodermal tissues and dose-dependent activation of both dorsal and ventrolateral mesodermal markers. At high doses mature Vg1 induced formation of “embryoids” with a rudimentary axial pattern, head structures including eyes, and a functional neuromuscular system. Furthermore, truncated forms of the activin and FGF receptors, which block mesoderm induction in the intact embryo, fully inhibited mature Vg1 activity. Follistatin, a specific inhibitor of activin βB which does not block endogenous mesoderm induction, failed to inhibit Vg1. The results support a role for endogenous Vgl in dorsal mesoderm induction during Xenopus development.