N-CADHERIN IS INVOLVED IN MYOBLAST MIGRATION AND MUSCLE DIFFERENTIATION IN THE AVIAN LIMB BUD

Limb muscle formation involves invasion of the limb bud mesoderm by my ogenic precursor cells from the dermomyotomes at limb bud level. Direc ted cell migration, homing, and differentiation of myogenic cells are controlled by the stationary cells of the Limb bud mesoderm. At the le vel of the extracellular matrix, the molecular basis of migration cont rol has been suggested to be exerted by the distribution of hyaluronan , Here, we demonstrate that N-cadherin-mediated interactions play a ro le at cell-membrane level in myoblast distribution and differentiation . N-cadherin is strongly expressed by myogenic cells in the chick Limb bud and more moderately expressed by stationary mesodermal cells in t he myogenic zones and progress zone, After in vivo injection of antibo dies and Fab-fragments against the hemophilic binding site of N-cadher in into the wing bud mesoderm, aggregates of myoblasts are found predo minantly in the dorsal myogenic zone 36 hr after injection apparently due to immobilization. In the same position, areas of myf-5-positive c ells are also observed. In injected limb buds, Pax-3-positive cells ar e less evenly distributed than in uninjected Limbs. They are found to spread up to the epidermis and also form loosely arranged aggregates. After prolonged reincubation periods, injected limbs show ectopic myob lasts that are rich in. desmin and areas of strongly desmin-expressing myoblasts within muscle blastemas. These effects were not observed af ter application of antibodies against other parts of the N-cadherin mo lecule. We conclude that N-cadherin is involved in myoblast migration in the limb buds via hemophilic interactions and that it plays a role in signal transduction during myogenesis. (C) 1996 Academic Press, Inc .