PAX-3 IS NECESSARY FOR MIGRATION BUT NOT DIFFERENTIATION OF LIMB MUSCLE PRECURSORS IN THE MOUSE

The limb muscles of vertebrates are derived from precursor cells that migrate from the lateral edge of the dermomyotome into the limb bud, P revious studies have shown that the paired domain-containing transcrip tion factor Pax-3 is expressed in the limb in cells that are precursor s for limb muscles (Williams, B. and Ordahl, C. P. (1994) Development 120, 785-796), In splotch (Pax-3(-)) embryos, the limb muscles fail to develop and cells expressing Pax-3 are no longer found in the limb, I n this paper we have analyzed the role of Pax-3 in the migration and s ubsequent differentiation of limb muscle precursors, By labeling somit es adjacent to the prospective forelimb with the lipophilic dye DiI, w e have shown that cells derived from these somites do not migrate into the limbs of splotch mice, The failure of limb muscle precursors to i nvade the limb in splotch mice is associated with the absence of c-met expression in premigratory cells, together with a change in the morph ology of the ventral dermomyotome, In addition, we have shown the late ral half of somites derived from day E9.25 splotch embryos can undergo muscle differentiation when grafted into the limb bud of stage 20 chi ck host embryos, Our results indicate that Pax-3 regulates the migrati on of limb muscle precursors into the limb and is not required for cel ls in the lateral somite to differentiate into muscle.