AbstractMolecules regulating morphogenesis by cell‐cell interactions are the cadherins, a class of calcium‐dependent adhesion molecules. One of its members, M‐cadherin, has been isolated from a myoblast cell line (Donalies et al. [1991] Proc. Natl. Acad. Sci. U.S.A. 88:8024—8028). In mouse development, expression of M‐cadherin mRNA first appears at day 8.5 of gestation (E8.5) in somites and has been postulated to be down‐regulated in developing muscle masses (Moore and Walsh [1993] Development 117:1409—1420). Affinity‐purified polyclonal M‐cadherin antibodies, detecting a protein of approximately 120 kDa, were used to study the cell 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 in myogenic cells of somitic origin. The detection of the protein at E10 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 during differentiation of ES cell line BLC6 into skeletal muscle cells in culture, expression of M‐cadherin mRNA can be detected 2 days prior to M‐cadherin protein. During prenatal development, the pattern of M‐cadherin expression changes: In E10 1/3 embryos and also in myotomal cells of later stages, M‐cadherin is evenly distributed on the cell surface. In developing muscle masses (tested at E16 to E18), however, M‐cadherin protein becomes clustered most likely at sites of cell‐cell contact as indicated by double‐labelling experiments: M‐cadherin‐staining is the positive image of laminin negative areas excluding the presence of a basal lamina at M‐cadherin positive sites. Furthermore, M‐cadherin is coexpressed with the neuronal cell adhesion molecule N‐CAM which has been shown to mediate cell‐cell contact in myogenic cells. In summary, our results are in line with the idea that M‐cadherin might play a central role in myogenic morphogenesis. © 1994 Wiley‐Liss, Inc.