N-CADHERIN PROMOTES THE COMMITMENT AND DIFFERENTIATION OF SKELETAL-MUSCLE PRECURSOR CELLS

Cells with the potential to form skeletal muscle are present in the ch ick embryo prior to gastrulation. Muscle differentiation begins after gastrulation within the somites. The role of cadherin-mediated adhesio n in the commitment and differentiation of skeletal muscle precursor c ells was examined by analyzing the expression of cell-cell adhesion mo lecules in cultures of epiblast, segmental plate, and somite cells and by determining the effects of adhesion-perturbing antibodies on the a ccumulation of MyoD and sarcomeric myosin. Cultured primitive streak s tage epiblast cells downregulate E-cadherin and upregulate N-cadherin. This switch in cadherin expression also occurs in vivo as epiblast ce lls enter the primitive streak. Although MyoD protein is present in ce lls with N- or E-cadherin, only cells with N-cadherin differentiate in to skeletal muscle. In contrast to the primitive streak stage epiblast cells, prestreak epiblast cells maintain the expression of E-cadherin in vitro. While the majority of prestreak cells contain MyoD, only a few synthesize myosin. Treatment of primitive streak stage epiblast ce lls with function-perturbing antibodies to N-cadherin resulted in an i nhibition of myosin accumulation and a decrease in the percentage of c ells with MyoD. Segmental plate and somite cells are similar to primit ive streak stage epiblast cells in that most differentiated into skele tal muscle when cultured in serum-free medium. While function-perturbi ng antibodies to N-cadherin inhibited the accumulation of myosin in th ese mesoderm cells, the number of MyoD positive cells was unaffected i n somite cultures and only partially reduced in segmental plate cultur es. These results suggest that N-cadherin-mediated cell-cell adhesion is involved in both the commitment of muscle precursors and their term inal differentiation. (C) 1997 Academic Press.