DISRUPTION OF BMP SIGNALS IN EMBRYONIC XENOPUS ECTODERM LEADS TO DIRECT NEURAL INDUCTION

Bone morphogenetic proteins (BMPs), which have been implicated in the patterning of mesoderm, are members of the transforming growth factor- beta (TGF-beta) superfamily. We have investigated the roles of Xenopus BMP-7 (XBMP-7) and BMP-4 (XBMP-4), and activin (another TGF-beta-rela ted molecule) in early development by generating dominant-negative ver sions of these growth factors. Mutations were generated by altering th e cleavage sites that are required for maturation of the active dimeri c forms of XBMP-7, XBMP-4, and activin. These mutant constructs, desig nated Cm-XBMP-7, Cm-XBMP-4, and Cm-activin, result in polypeptides tha t allow for dimerization of the subunits, but are incapable of maturat ion. Expression of Cm-XBMP-7 and Cm-XBMP-4, but not Cm-activin, in the ventral marginal zone of the Xenopus embryo results in the developmen t of a secondary axis, similar to that seen by ectopic expression of t he truncated BMP receptor. These results suggest that the cleavage mut ants interfere with BMP signaling during mesodermal patterning. We als o found that expression of Cm-XBMP-7 or Cm-XBMP-4 in animal cap ectode rm directly induces neuroectoderm The neural induction was specific fo r Cm-XBMP-7 and Cm-XBMP-4 because ectopic expression of Cm-activin or Vg-l did not mimic the same phenotype. Molecular study of neural patte rning by Cm-XBMP-7 and Cm-XBMP-4 revealed that only anterior neuroecto dermal markers are expressed in response to these Cm-XBMPs. These resu lts suggest that the BMPs are involved in the specification of ectoder m in Xenopus development, and that neural induction requires the remov al of BMP signals in the ectoderm. We propose that neural induction oc curs by a default mechanism, whereby the inhibition of BMP signaling i s required for the conversion of ectoderm to neuroectoderm in the deve loping Xenopus embryo.