Activin signalling has a necessary function in Xenopus early development

The first signalling event in Xenopus development is the mesoderm-forming (or Nieuwkoop) induction, starting three hours after fertilization [1]. Two prime candidates for the molecule that mediates this signalling are activin [2] and Vg1 [3], both members of the transforming growth factor beta (TGFbeta) family. Because genetic methods are not available for amphibian studies, 'dominant-negative' truncated receptors have been used in studying signalling molecules such as the receptors for fibroblast and platelet-derived growth factors (FGF and PDGF) [4] [5]. The truncated receptors bind to, and prevent signalling from, endogenous receptors. Activin is a potent mesoderm inducer in vitro, and the severe phenotype obtained using a dominant-negative activin receptor in Xenopus [6], coupled with evidence from fish [7], suggested that activin is essential for development. However, a dominant-negative receptor for activin blocked the activity of other TGFbeta family members in Xenopus, most notably Vg1 [8], and activin 'knock-out' mice are essentially wild-type in phenotype [7]; these two findings cast doubt on the idea of a function for activin in early development. We have designed a new receptor construct which can selectively block the function of activin but not of Vg1, and we have used it to show that activin has an essential role in vivo in Xenopus early development. We conclude that activin, or a close relative that has yet to be described, is required for normal development.