Control of muscle precursor cell migration by inductive and cell autonomous signals

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In the last application we have shown that the homeobox gene Lbx1 determines the migratory routes of muscle precursor cells in a cell autonomous manner. Our results demonstrated that Lbx1 is a key regulator of muscle precursor cell migration and required for targeted migration of precursor cells of hind limb muscles and extensor muscle of forelimbs. Ectopic expression of Lbx1 induced expression of muscle cell markers indicating that Lbx1 may have a dual role in controlling both the migration behavior of muscle precursor cells and the determination of their fate. Furthermore, we have unveiled a role of shh in the maintenance of hypaxial muscle cells and the formation of specific muscle groups derived from migratory precursor cells. In the next period we will investigate how Lbx1 specifies the migration path of subsets of limb muscle precursor cells. In particular, we will isolate heterozygous and homozygous Lbx1 expressing cells using the knocked-in LacZ gene and identify putative target genes of Lbx1. The contribution of cell autonomous information for targeted cell migration will be analyzed in xenotransplants of somites from heterozygous and homozygous mice into chicken host embryos. In addition, we will continue our efforts to characterize the role of secreted and membranebound molecules to direct migration of limb bud precursor cells. We will also generate double homozygous Lbx1/Mox2 and Lbx1/Pitx1 mutant mice to analyze compensatory regulatory pathways and differences in the migration of cells toward fore limb and hind limb.