The role of SF/HGF and c-Met in the development of skeletal muscle

Hypaxial skeletal muscles develop from migratory and non-migratory precurso r cells that are generated by the lateral lip of the dermomyotome, Previous work shows that the formation of migratory precursors requires the c-Met a nd SF/HGF genes. We show here that in mice lacking c-Met or SF/HGF, the ini tial development of the dermomyotome proceeds appropriately and growth and survival of cells in the dermomyotome are not affected. Migratory precursor s are also correctly specified, as monitored by the expression of Lbx1, How ever, these cells remain aggregated and fail to take up long range migratio n. We conclude that parallel but independent cues converge on the migratory hypaxial precursors in the dermomyotomal lip after they are laid down: a s ignal given by SF/HGF that controls the emigration of the precursors, and a n as yet unidentified signal that controls Lbx1. SF/HGF and c-Met act in a paracrine manner to control emigration, and migratory cells only dissociate from somites located close to SF/HGF-expressing cells. During long range m igration, prolonged receptor-ligand-interaction appears to be required, as SF/HGF is expressed both along the routes and at the target sites of migrat ory myogenic progenitors, Mice that lack c-Met die during the second part o f gestation due to a placental defect. Rescue of the placental defect by ag gregation of tetraploid (wild type) and diploid (c-Met(-/-)) morulae allows development of c-Met mutant animals to term. They lack muscle groups that derive from migratory precursor cells, but display otherwise normal skeleta l musculature.