DIFFERENTIAL-EFFECTS ON XENOPUS DEVELOPMENT OF INTERFERENCE WITH TYPEIIA AND TYPE IIB ACTIVIN RECEPTORS

One candidate for a mesoderm-inducing factor in early amphibian develo pment is activin, a member of the TGF beta family. Overexpression of a truncated form of an activin receptor Type IIB abolishes activin resp onsiveness and mesoderm formation in vivo. The Xenopus Type IIA activi n receptor XSTK9 differs from the Type IIB receptor by 43 and 25% in e xtracellular and intracellular domains respectively, suggesting the po ssibility of different functions in vivo. In this paper, we compare th e Type IIA receptor with the Type IIB to test such a possibility Simpl e overexpression of the wild-type receptors reveals minimal difference s, but experiments with dominant negative mutants of each receptor sho w qualitatively distinct effects. We show that while truncated (kinase domain-deleted) Type IIB receptors cause axial defects as previously described, truncated type IIA receptors cause formation of secondary a xes, similar to those seen by overexpression of truncated receptors fo r BMP-4, another TGF beta family member. Furthermore, in animal cap as says, truncated type IIB receptors inhibit induction of all mesodermal markers tested, while truncated type TIA receptors suppress induction only of ventral markers; the anterior/dorsal marker goosecoid is virt ually unaffected. The suppression of ventral development by the type I IA truncated receptor suggests either that the truncated Type IIA rece ptor interferes with ventral BMP pathways, or that activin signaling t hrough the Type IIA receptor is necessary for ventral patterning. (C) 1997 Elsevier Science Ireland Ltd.