BMP-2 -4 AND WNT-8 COOPERATIVELY PATTERN THE XENOPUS MESODERM/

Establishment of the dorsoventral axis is central to animal embryonic organization. In Xenopus two different classes of signaling molecules function in the dorsoventral patterning of the mesoderm. Both the TGF- beta-related products of the BMP-2 and BMP-4 genes and the Wnt molecul e encoded by Xenopus Wnt-8 specify ventral fate and appear to inhibit dorsal mesodermal development. The similar functions of these molecula rly very different classes of signaling molecules prompted us to study their mutual regulation and to closely compare their roles in mesoder m patterning. We find that Wnt-8 and BMP-4 are indistinguishable in th eir abilities to induce expression of ventral genes. Although BMP-2/-4 signaling regulates Wnt-8 expression, these genes do not function in a linear pathway because Wnt-8 overexpression cannot compensate for an inhibition of BMP-2/-4 function, but rather BMP-4 overexpression resc ues ventral gene expression in embryos with inhibited Wnt-8 function. We further find that Wnt-8 and BMP-2/-4 differ in their abilities to r egulate dorsal gene expression. While BMP4 appears to generally inhibi t the expression of dorsal genes, Xenopus Wnt-8 only inhibits the expr ession of the notochord marker Xnot. Whereas the inhibitory effect of BMP-2/-4 localizes dorsal mesodermal fate, our results suggest that Xe nopus Wnt-8 functions in the further patterning of the dorsal mesoderm into the most dorsal sector from which the notochord develops and the dorsolateral sector from where the somites differentiate. (C) 1998 El sevier Science Ireland Ltd.