Rib Truncations and Fusions in the Sp2HMouse Reveal a Role for Pax3 in Specification of the Ventro-lateral and Posterior Parts of the Somite

AbstractThesplotch (Pax3)mouse mutant serves as a model for developmental defects of several types, including defective migration of dermomyotomal cells to form the limb musculature. Here, we describe abnormalities of the ribs, neural arches, and acromion inSp2Hhomozygous embryos, indicating a widespread dependence of lateral somite development onPax3function. Moreover, the intercostal and body wall muscles, derivatives of the ventrolateral myotome, are also abnormal inSp2Hhomozygotes.Pax3is expressed in the dermomyotome, but not in either the sclerotome or the myotome, raising the possibility thatPax3-dependent inductive influences from the dermomyotome are necessary for early specification of lateral sclerotome and myotome. Support for this idea comes from analysis of gene expression markers of lateral sclerotome (tenascin-Candscleraxis) and myotome (myogenin, MyoD,andMyf5). All exhibit ventrally truncated domains of expression inSp2Hhomozygotes, potentially accounting for the rib and intercostal muscle truncations. In contrast, the medial sclerotomal markerPax1is expressed normally in mutant embryos, arguing thatPax3is not required for development of the medial sclerotome. Most of the somitic markers show ectopic expression in anteroposterior and mediolateral dimensions, suggesting a loss of definition of somite boundaries insplotchand explaining the rib and muscle fusions. An exception isMyf5,which is not ectopically expressed inSp2Hhomozygotes, consistent with the previous suggestion thatPax3andMyf5function in different pathways of skeletal myogenesis. PDGFα and its receptor are candidates for mediating signalling between myotome and sclerotome. We find that both genes are misexpressed inSp2Hembryos, suggesting that PDGFα/PDGFRα may function downstream ofPax3,accounting for the close similarities between thesplotchandPatchmutant phenotypes. Our findings point to additional regulatory functions for the Pax3 transcription factor, apart from those already demonstrated for development of the neural tube, neural crest, and dermomyotome