Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites

Abstract

The paired box containing transcription factor Pax3 is a crucial regulator of dermomyotome and muscle development. However, the allelic series of Pax3/Splotch mutants also displays characteristic vertebral column malformations, which do not result from defective dorsoventral somite pattern. Rather, vertebral column and sclerotomal phenotypes are reminiscent of the phenotypes observed in the segmentation/somitogenesis mutants rachiterata and pudgy. Moreover, rostrocaudal somite pattern and somitic boundaries are disturbed in Splotch as monitored by the expression of Uncx4.1 and Lunatic fringe. Alterations in EphA4, Dll1, and Uncx4.1 expression are evident already in the condensing paraxial mesoderm, correlating with the first phase of Pax3 expression before and during somite formation. This finding suggests an early function of Pax3 during the formation of epithelial somites.

T-box Protein Tbx18 Interacts with the Paired Box Protein Pax3 in the Development of the Paraxial Mesoderm

“…This is in contrast to studies where lethality of Pax3 Ϫ/Ϫ embryos was observed between E13.5 and E14.5 when the mutant allele was kept on an inbred background, such as a mix of C3H/101 and BA/Ca or C57Bl6 (17,18). Tbx18 Ϫ/Ϫ embryos died shortly after birth as reported before (12).…”

“…4F, arrow). However, skeletal defects were generally less severe than the ones described for Pax3 alleles maintained on inbred genetic backgrounds (17,18). Notably, and in contrast to Tbx18 mutants, the proximal ribs were unaffected, and the pedicles were spaced regularly (Fig.…”

Cell-type-specific regulation of distinct sets of gene targets by Pax3 and Pax3/FKHR

“…We also focused on Pax3 or Pax3/FKHR target genes known or likely to be genetically downstream of Pax3. For example, Pax3 is required for proper epithelialization of the developing somite (Schubert et al, 2001). EPHA4, which is normally expressed in the anterior portion of newly formed somites, is misexpressed in Pax3-deficient embryos (Schubert et al, 2001).…”

Pax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage

“…p.c.) in the myotome [33,34]. Pax3 is also present in the brain, dorsally throughout the neural tube and in neural crest cells.…”