DISRUPTION OF GASTRULATION MOVEMENTS IN XENOPUS BY A DOMINANT-NEGATIVE MUTANT FOR C-CADHERIN

Gastrulation in Xenopus laevis transforms a ball of undifferentiated cells into a well-organized elongated embryo with a distinct body axis, as a result of extensive cell rearrangements and movements. Since cell adhesion is thought to play an important role during tissue morphogenesis, we investigated the potential role for C-cadherin, a primary cell-cell adhesion molecule in Xenopus, in gastrulation movements. A deletion mutant consisting of the extracellular and transmembrane domains but lacking the cytoplasmic tail (Ctrunc) was constructed to act as a dominant-negative inhibitor of the endogenous protein. Injection of in vitro transcribed Ctrunc mRNA into the prospective dorsal involuting marginal zone, the region that undergoes the most extensive movements, caused a reproducible defect in gastrulation. The defect, an inability to complete involution and close the blastopore, was cadherin-specific, because it could be rescued by expressing full length C-cadherin. Ctrunc also seems to inhibit morphogenetic movements of animal cap explants isolated from injected embryos. Expression of Ctrunc did not appear to interfere with inductive processes in the embryos that developed gastrulation defects, because they formed complete axial structures, including a complete head and notochord. These results demonstrate that C-cadherin plays a critical role in Xenopus laevis gastrulation movements, and they support the hypothesis that cadherins can mediate cellular rearrangements during tissue morphogenesis. (C) 1995 Academic Press, Inc.