| First Author | Henderson DJ | Year | 1999 |
| Journal | Dev Biol | Volume | 209 |
| Issue | 1 | Pages | 143-58 |
| PubMed ID | 10208749 | Mgi Jnum | J:54638 |
| Mgi Id | MGI:1335652 | Doi | 10.1006/dbio.1999.9215 |
| Citation | Henderson DJ, et al. (1999) Rib truncations and fusions in the Sp2H mouse reveal a role for Pax3 in specification of the ventro-lateral and posterior parts of the somite. Dev Biol 209(1):143-58 |
| abstractText | The splotch (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 in Sp(2H) homozygous embryos, indicating a widespread dependence of lateral somite development on Pax3 function. Moreover, the intercostal and body wall muscles, derivatives of the ventrolateral myotome, are also abnormal in Sp(2H) homozygotes. Pax3 is expressed in the dermomyotome, but not in either the sclerotome or the myotome, raising the possibility that Pax3-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-C and scleraxis) and myotome (myogenin, MyoD, and Myf5). All exhibit ventrally truncated domains of expression in Sp(2H) homozygotes, potentially accounting for the rib and intercostal muscle truncations. In contrast, the medial sclerotomal marker Pax1 is expressed normally in mutant embryos, arguing that Pax3 is not required for development of the medial sclerotome. Most of the semitic markers show ectopic expression in anteroposterior and mediolateral dimensions, suggesting a loss of definition of somite boundaries in splotch and explaining the rib and muscle fusions. An exception is Myf5, which is not ectopically expressed in Sp(2H) homozygotes, consistent with the previous suggestion that Pax3 and Myf5 function in different pathways of skeletal myogenesis. PDGF alpha and its receptor are candidates for mediating signalling between myotome and sclerotome. We find that both genes are misexpressed in Sp(2H) embryos, suggesting that PDGF alpha/ PDGFR alpha may function downstream of Pax3, accounting for the close similarities between the splotch and Patch mutant 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. (C) 1999 Academic Press. |
