ACTIVIN SIGNALING HAS A NECESSARY FUNCTION IN XENOPUS EARLY DEVELOPMENT

The first signalling event in Xenopus development is the mesoderm form ing (or Nieuwkoop) induction, starting three hours after fertilization [1]. Two prime candidates for the molecule that mediates this signall ing are activin [2] and Vg1 [3], both members of the transforming grow th factor beta (TGF beta) family. Because genetic methods are not avai lable for amphibian studies, 'dominant-negative' truncated receptors h ave been used in studying signalling molecules such as the receptors f or fibroblast and platelet derived growth factors (FGF and PDGF) [4,5] . The truncated receptors bind to, and prevent signalling from, endoge nous 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 ac tivin is essential for development. However, a dominant-negative recep tor for activin blocked the activity of other TGF beta family members in Xenopus, most notably Vg1 [8], and activin 'knock-out' mice are ess entially wild type in phenotype [7]; these two findings cast doubt on the idea of a function for activin in early development. We have desig ned 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 ha s an essential role in vivo in Xenopus early development, We conclude that activin, or a close relative that has yet to be described, is req uired for normal development.