CONTRIBUTION OF CADHERINS TO DIRECTIONAL CELL-MIGRATION AND HISTOGENESIS IN XENOPUS EMBRYOS

Perturbation of adhesion mediated by cadherins was achieved by over-ex pressing truncated forms of E- and EP-cadherins (in which the extracel lular domain was deleted) in different blastomeres of stage 6 Xenopus laevis embryos. Injections of mRNA encoding truncated E- and EP-cadher ins into A1A2 blastomeres resulted in inhibition of cell adhesion and, at later stages, in morphogenetic defects in the anterior neural tiss ues to which they mainly contribute. In addition, truncated EP-cadheri n mRNA produced a duplication of the dorso-posterior axis in a signifi cant number of cases. The expression of truncated E- and EP-cadherins in blastomeres involved in gastrulation and neural induction (B1B2 and C1), led to the duplication of the dorso-posterior axis as well as to defects in anterior structures. Morphogenetic defects obtained with t runcated EP-cadherin were more severe than those induced with truncate d E-cadherin. Cells derived from blastomeres injected with truncated E P-cadherin mRNA, dispersed more readily at the blastula and gastrula s tages than the cells derived from the blastomeres expressing truncated E-cadherin. Presumptive mesodermal cells expressing truncated cadheri ns did not engage in coherent directional migration. The alteration of cadherin-mediated cell adhesion led directly to the perturbation of t he convergent-extension movements during gastrulation as shown in the animal cap assays and indirectly to perturbation of neural induction. Although the cytoplasmic domains of type I cadherins share a high degr ee of Sequence identity, the over-expression of their cytoplasmic doma ins induces a distinct pattern of perturbations, strongly suggesting t hat in vivo, each cadherin may transduce a specific adhesive signal. T hese graded perturbations may in part result from the relative ability of each cadherin cytoplasmic domain to titer the beta-catenin.