N-CADHERIN CATENIN-MEDIATED MORPHOREGULATION OF SOMITE FORMATION/

Somitogenesis during early stages in the chick and mouse embryo was ex amined in relation to N-cadherin-mediated adhesion. Previous studies i ndicated that N-cadherin localizes to the somite regions during their formation. Those observations were extended to include a spatiotempora l immunohistochemical analyses of beta-catenin and alpha-catenin, as w ell as a more detailed study of N-cadherin, during segmentation, compa ction, and compartmentalization of the somite. N-cadherin and the cate nins appear early within the segmental plate and are expressed as smal l patch-like foci throughout this tissue. The small foci of immunostai ning coalesce into larger clusters of N-cadherin/catenin-expressing re gions. The clusters subsequently coalesce into a region of centrally l ocalized cells that express N-cadherin/catenins at their apical surfac es. The multiple clusters are spaced wide apart in the anterior segmen tal plates that form the first 6 somite pairs, as contrasted to segmen tal plates that form somites 7 and beyond. To examine the functional s ignificance of N-cadherin, segmental plates were exposed to antibodies that perturb N-cadherin-mediated adhesion in the chick embryo. The mu ltiple, anomalous somites that result in these experiments indicate th at each N-cadherin/catenin-expressing cluster can give rise to a semit ic structure. beta-Catenin involvement in somitogenesis suggests a rol e for Wnt-mediated signaling. Embryos treated with LiCl also show indu ction of similar anomalous somites indicating further the possibility that Wnt-mediated signaling may be involved in the clustering event. I t is suggested that beta-catenin serves to initiate the adhesion proce ss which is spread then by N-cadherin. Later during compartmentalizati on, N-cadherin/catenins remain expressed by the myotome compartment. T aken together, these results suggest that the Ca2+-dependent cell adhe sion molecule N-cadherin and the intracellular catenins are important in segmentation and formation of the somite and myotome compartment. I t is proposed that the N-cadherin-mediated adhesion process may serve as a common, evolutionarily conserved, link in the differentiation pat hways of skeletal and cardiac muscle. (C) 1998 Academic Press.