Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud

Abstract

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.