A POTENTIAL ROLE OF R-CADHERIN IN STRIATED-MUSCLE FORMATION

We have examined the murine embryonic expression pattern of the cell a dhesion molecule R-cadherin in muscle,, kidney, thymus, and lung. In d eveloping muscle, R-cadherin was first seen at 10.5-11.5 days postcoit um in the semitic myotome. Consistently, we found R-cadherin expressed at the highest levels in the myotome, early skeletal muscle, and smoo th muscle (both vascular and visceral), while very low levels of R-cad herin were detected in the heart. The expression pattern and subcellul ar localization of R-cadherin in developing skeletal muscle indicate a possible role in myoblast cell-cell interactions during both primary and secondary myogenesis. In the developing kidney, R-cadherin was fir st detected at 10.5 days postcoitum in the mesonephric epithelial tubu le cells. In the metanephric kidney, it was specifically expressed in the pretubular aggregates, comma- and S-shaped bodies, proximal tubule s, and collecting ducts. Thus, in the kidney, R-cadherin was associate d with the mesenchymal-epithelial transition. R-cadherin was also foun d in other developing epithelia, for example in the thymic epithelial cells. In the lung, R-cadherin was expressed at the highest levels in the smooth muscle surrounding the lung epithelial tubules. To test whe ther R-cadherin can direct formation of tissues, we constitutively exp ressed R-cadherin in E-cadherin-/-ES cells and examined histogenesis i n teratomas derived from these cells. R-cadherin exclusively rescued f ormation of striated muscle and epithelia in the teratomas. R-cadherin 's ability to form epithelia in vivo was substantiated by its ability to rescue formation of cystic embryoid bodies in vitro. By comparing o ur data with the previously reported embryonic expression patterns and histogenetic activities of E- and N-cadherin, we suggest that R-cadhe rin plays an important role in the formation of striated muscle and po ssibly also of epithelia. (C) 1997 Academic Press.