Migration of cells plays a critical role in the genesis of many tissues during embryonic development and in tumor metastases. The migration of muscle precursors provides an ideal model system to study the mechanisms that control cell migration in vertebrates. Most muscles in the vertebrate body are derived from migratory precursors that undergo long range cell migration from the somites. Hypaxial muscle precursors leave the ventral dermomyotome and migrate along a lateral route into the limbs to give rise to limb muscles and along ventral routes into the branchial arches and septum transversum to form the tongue and diaphragm muscles, respectively. We have a long term interest in understanding how the migration of these muscle precursors is regulated, since the mechanisms that operate in these cells are likely to apply to other migratory cell populations. Our studies have been directed toward functionally analyzing the role of two transcription factors, Pax3 and Lbxl, in the development of muscles. With this grant, we will dissect early specification and late migration roles of Pax3 in the genesis of hypaxial muscles. Second, we will examine the Lbxl dependent response to a lateral migration cue by a series of explant and misexpression experiments. Third, we will examine which components of FGF signaling are involved in the lateral migration of appendicular muscle precursors. Finally, we will initiate a search for genes that are selectively expressed in migrating muscle precursor cells to identify signaling pathways and proteins that control cell migration .
