A crucial role for Pax3 in the development of the hypaxial musculature and the long-range migration of muscle precursors.

Activated by dorsalizing and lateralizing signals, the Pax3 gene is an early marker for the entire paraxial mesoderm and its dorsal derivative, the dermomyotome. Later, its expression becomes restricted to the lateral dermomyotome and to the migratory muscle precursors giving rise to the hypaxial musculature. To understand better the role that Pax3 plays during development of paraxial mesoderm-derived structures, we followed the development of the musculature and skeleton in the murine Pax3 mutant Splotch. We found that the mutant dermomyotomes and myotomes failed to organize and to elongate medially and laterally, leading to the reduction and malformation of the entire trunk musculature. Mutants lacked ventral aspects of the body wall musculature and muscles derived from migratory myoblasts, suggesting a crucial function for Pax3 in the long-range migration of muscle precursors giving rise to the ventral hypaxial musculature. In addition, severe malformations were detected in the skeleton. The axial and appendicular skeleton displayed malformations and in particular multiple bone fusions.