EXPRESSION OF M-CADHERIN PROTEIN IN MYOGENIC CELLS DURING PRENATAL MOUSE DEVELOPMENT AND DIFFERENTIATION OF EMBRYONIC STEM-CELLS IN CULTURE

Molecules regulating morphogenesis by cell-cell interactions are the c adherins, a class of calcium-dependent adhesion molecules. One of its members, M-cadherin, has been isolated from a myoblast cell line (Dona lies et al. [1991] Proc. Natl. Acad. Sci. U.S.A. 88:8024-8028). In mou se development, expression of M-cadherin mRNA first appears at day 8.5 of gestation (E8.5) in somites and has been postulated to be downregu lated in developing muscle masses (Moore and Walsh [1993] Development 117:1409-1420). Affinity-purified polyclonal M-cadherin antibodies, de tecting a protein of approximately 120 kDa, were used to study the cel l expression pattern of M-cadherin protein. It was first visualized in somites at E10 1/3 and could be confined to desmin positive, myotomal cells. At all subsequent prenatal stages, M-cadherin was only found i n myogenic cells of semitic origin. The detection of the protein at E1 0 1/3 suggests a translational delay of M-cadherin mRNA of 1 to 2 days (E8.5 vs. E10 1/3). This was further supported by the finding that du ring differentiation of ES cell line BLC6 into skeletal muscle cells i n culture, expression of M-cadherin mRNA can be detected 2 days prior to M-cadherin protein. During prenatal development, the pattern of M-c adherin expression changes: In E10 1/3 embryos and also in myotomal ce lls of later stages, M-cadherin is evenly distributed on the cell surf ace. In developing muscle masses (tested at E16 to E18), however, M-ca dherin protein becomes clustered most likely at sites of cell-cell con tact as indicated by double-labelling experiments: M-cadherin-staining is the positive image of laminin negative areas excluding the presenc e of a basal lamina at M-cadherin positive sites. Furthermore, M-cadhe rin is coexpressed with the neuronal cell adhesion molecule N-CAM whic h has been shown to mediate cell-cell contact in myogenic cells. In su mmary, our results are in line with the idea that M-cadherin might pla y a central role in myogenic morphogenesis. (C) 1994 Wiley-Liss, Inc.