ESSENTIAL ROLE FOR THE C-MET RECEPTOR IN THE MIGRATION OF MYOGENIC PRECURSOR CELLS INTO THE LIMB BUD

LIMB muscles develop from cells that migrate from the somites(1,2). The signal that induces migration of myogenic precursor cells to the limb emanates from the mesenchyme of the limb bud(2,3). Here we report that the c-met-encoded receptor tyrosine kinase is essential for migration of myogenic precursor cells into the limb anlage and for migration into diaphragm and tip of tongue. In c-met homozygous mutant (-/-) mouse embryos, the limb bud and diaphragm are not colonized by myogenic precursor cells and, as a consequence, skeletal muscles of the limb and diaphragm do not form. In contrast, development of the axial skeletal muscles proceeds in the absence of c-met signalling. The specific ligand of the c-met protein, the motility and growth factor scatter factor/hepatocyte growth factor(4-9), is expressed in limb mesenchyme and can thus provide the signal for migration which is received by c-met. We have therefore identified a paracrine signalling system that regulates migration of myogenic precursor cells.