IDENTIFICATION OF DISTINCT CLASSES AND FUNCTIONAL DOMAINS OF WNTS THROUGH EXPRESSION OF WILD-TYPE AND CHIMERIC PROTEINS IN XENOPUS EMBRYOS

Wnts are secreted signaling factors which influence cell fate and cell behavior in developing embryos. Overexpression in Xenopus laevis embr yos of a Xenopus Wnt, Xwnt-8, leads to a duplication of the embryonic axis. In embryos ventralized by UV irradiation, Xwnt-8 restores expres sion of the putative transcription factor goosecoid, and rescues norma l axis formation. In contrast, overexpression of Xwnt-5A in normal emb ryos generates defects in dorsoanterior structures, without inducing g oosecoid or a secondary axis. To determine whether Xwnt-4 and Xwnt-11 fall into one of these two previously described classes of activity, s ynthetic mRNAs were introduced into animal caps, normal embryos, and U V-treated embryos. The results indicate that Xwnt-4, Xwnt-5A, and Xwnt -11 are members of a single functional class with activities that are indistinguishable in these assays. To investigate whether distinct reg ions of Xwnt-8 and Xwnt-SA were sufficient for eliciting the observed effects of overexpression, we generated a series of chimeric Xwnts. RN As encoding the chimeras were injected into normal and UV-irradiated X enopus embryos. Analysis of the embryonic phenotypes and goosecoid lev els reveals that chimeras composed of carboxy-terminal regions of Xwnt -8 and amino-terminal regions of Xwnt-5A are indistinguishable from th e activities of native Xwnt-8 and that the reciprocal chimeras elicit effects indistinguishable from overexpression of native Xwnt-5A. We co nclude that the carboxy-terminal halves of these Xwnts are candidate d omains for specifying responses to Xwnt signals.