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). Th e signal that induces migration of myogenic precursor cells to the lim b emanates from the mesenchyme of the limb bud(2,3). Here we report th at the c-met-encoded receptor tyrosine kinase is essential for migrati on of myogenic precursor cells into the limb anlage and for migration into diaphragm and tip of tongue. In c-met homozygous mutant (-/-) mou se embryos, the limb bud and diaphragm are not colonized by myogenic p recursor 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 lig and of the c-met protein, the motility and growth factor scatter facto r/hepatocyte growth factor(4-9), is expressed in limb mesenchyme and c an thus provide the signal for migration which is received by c-met. W e have therefore identified a paracrine signalling system that regulat es migration of myogenic precursor cells.