PAX-3 IS REQUIRED FOR THE DEVELOPMENT OF LIMB MUSCLES - A POSSIBLE ROLE FOR THE MIGRATION OF DERMOMYOTOMAL MUSCLE PROGENITOR CELLS

Limb muscles in vertebrates originate from dermomyotomal cells, which during early development migrate from the ventrolateral region of somi tes into the limb buds. These progenitor cells do not express any musc le-specific marker genes or myogenic transcription factors until they reach their destination in the limbs. Here, we demonstrate by in situ hybridization that myogenic cells in somites and a population of presu mably migratory muscle precursor cells in somatopleural tissue as well as myoblasts in the developing limbs express Pax-3. Significantly, in homzygous splotch mutant mice, which synthesize altered Pax-3 mRNA bu t make no normal protein, no cells positive for Pax-3 transcripts can be detected in the region of migrating limb muscle precursors or in th e limb itself. In contrast, myotomal precursor cells and axial skeleta l muscles contain Pax-3 transcripts also in the mutant. Interestingly, these animals fail to develop limb musculature as demonstrated by the lack of hybridization with various probes for myogenic transcription factors (Myf-5, myogenin, MyoD) but make apparently normal axial muscl es. These observations suggest that Pax-3 is necessary for the formati on of limb muscles, affecting either the generation of myogenic precur sors in the semitic dermomyotome or the migration of these cells into the limb field.