WNT4 AFFECTS MORPHOGENESIS WHEN MISEXPRESSED IN THE ZEBRAFISH EMBRYO

The Wnts are a family of secreted glycoproteins involved in cell-cell signalling and pattern formation during development, although the exte nt to which various Wnts are functionally equivalent remains unclear. We have cloned zebrafish (Danio rerio) wnt4, characterized its express ion, and compared its activity relative to other Wnts. The wnt4 transc ript is first detected early in somitogenesis, in the dorsocaudal regi on of the forebrain, and then appears in the dorsal and lateral region s of the caudal hindbrain and neural keel. During somitogenesis, wnt4 appears in the floor plate, and this expression is absent in cyclops m utants, which lack floor plate. wnt4 is also expressed in the developi ng pronephros and gill slit. To characterize the biological activity o f wnt4, synthetic zebrafish wnt4 mRNA was injected into embryos of zeb rafish and Xenopus laevis. The phenotypic effects of misexpression in the zebrafish include cyclopia, misfolding in the brain, and an anteri orly forking notochord. Comparison of the phenotypes arising from mise xpression of wnt4 and Xwnt-5A in both organisms suggests close paralle ls in the response to these Wnts. Our data suggest that wnt4, like Xwn t-5A, inhibits cell movements, and that these Wnts define a functional class distinct from the class which includes Wnt-1, Xwnt-3A and Xwnt- 8.