N-CADHERIN-CATENIN INTERACTION - NECESSARY COMPONENT OF CARDIAC CELL COMPARTMENTALIZATION DURING EARLY VERTEBRATE HEART DEVELOPMENT

During early heart development the expression pattern of N-cadherin, a calcium-dependent cell adhesion molecule, suggests its involvement in morphoregulation and the stabilization of cardiomyocyte differentiati on. N-cadherin's adhesive activity is dependent upon its interaction w ith the intracellular catenins. An association with alpha-catenin and beta-catenin also is believed to be involved in cell signaling. This s tudy details the expression patterns of alpha-catenin, beta-catenin, a nd gamma-catenin, during definition of the cardiac cell population as distinct compartments in the anterior regions of the chick embryo betw een stages 5 and 9. The restriction of N-cadherin/catenin localization at stage 5+ from a uniform pattern in vive, to specific cell clusters that demarcate areas where mesoderm separation is initiated, suggests that the N-cadherin/catenin complex is involved in boundary formation and in the subsequent cell sorting. The latter two processes lead to the specification and formation of the somatic and cardiac splanchnic mesoderm. N-cadherin colocalized with alpha- and beta-catenin at the c ell membrane before and during the time that its expression becomes re stricted to the lateral mesoderm and continues cephalocaudad into stag e 8. These proteins continue to colocalize in the myocardium of the tu bular heart. Plakoglobin is not expressed in this region during stages 6-8, but is detected in the myocardium later at stage 13. The observe d in vive expression patterns of alpha-catenin, beta-catenin, and plak oglobin suggest that these proteins are directly linked with the devel opmental regulation of cell junctions, as cardiac cells become stably committed and phenotypically differentiated to eventually form a matur e myocardium. The localization of N-CAM also was analyzed during these stages to determine whether the N-cadherin-catenin localization was u nique or whether other cell adhesion molecules were expressed similarl y. The results indicate that the unique pattern of N-cadherin expressi on is not shared with N-CAM. We also show that perturbation of N-cadhe rin using a function perturbing N-cadherin antibody (NCD-2) inhibits n ormal early heart development and myogenesis in a cephalocaudad, stage -dependent manner. We propose a model whereby myocardial cell compartm entalization also defines the endocardial population. The presence of beta-catenin suggests that a similar signaling pathway involving Wnt ( wingless)-mediated events may function in myocardial cell compartmenta lization during early vertebrate heart development, as in Drosophila c ontractile vessel development. (C) 1997 Academic Press.