Identification of Distinct Classes and Functional Domains of Wnts through Expression of Wild-Type and Chimeric Proteins in Xenopus Embryos

Abstract

Wnts are secreted signaling factors which influence cell fate and cell behavior in developing embryos. Overexpression in Xenopus laevis embryos of a Xenopus Wnt, Xwnt-8, leads to a duplication of the embryonic axis. In embryos ventralized by UV irradiation, Xwnt-8 restores expression of the putative transcription factor goosecoid, and rescues normal axis formation. In contrast, overexpression of Xwnt-5A in normal embryos generates defects in dorsoanterior structures, without inducing goosecoid or a secondary axis. To determine whether Xwnt-4 and Xwnt-11 fall into one of these two previously described classes of activity, synthetic mRNAs were introduced into animal caps, normal embryos, and UV-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 regions of Xwnt-8 and Xwnt-5A were sufficient for eliciting the observed effects of overexpression, we generated a series of chimeric Xwnts. RNAs encoding the chimeras were injected into normal and UV-irradiated Xenopus embryos. Analysis of the embryonic phenotypes and goosecoid levels reveals that chimeras composed of carboxy-terminal regions of Xwnt-8 and amino-terminal regions of Xwnt-5A are indistinguishable from the activities of native Xwnt-8 and that the reciprocal chimeras elicit effects indistinguishable from overexpression of native Xwnt-5A. We conclude that the carboxy-terminal halves of these Xwnts are candidate domains for specifying responses to Xwnt signals.

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

“…Wnt3 belongs to the Wnt1 class of ligands and stimulates the canonical Wnt/β-catenin pathway [45]. Enhanced Wnt3 gene expression has been reported in A549 (lung), MKN45 (gastric), and human breast and rectal tumors [46].…”

When pathways collide: collaboration and connivance among signalling proteins in development

“…Wnt ligands have been traditionally subdivided into canonical and non-canonical groups, based on their ability to induce a secondary body axis in Xenopus and to transform C57MG epithelial cells reflecting β-catenin signalling 36,37 . Wnt1, Wnt-3a and Wnt-8 thus have been suggested to act through the canonical pathway (i.e.…”

Wnts as ligands: processing, secretion and reception

“…In Xenopus, WNT11 was long thought to solely induce non-canonical convergence extension movements (Du et al, 1995;Djiane et al, 2000). However, recent evidence shows that maternally contributed WNT11 actually serves as the key canonical Wnt signaling initiating factor during axis formation in the early Xenopus embryo (Tao et al, 2005).…”