The bHLH class protein pMesogenin1 can specify paraxial mesoderm phenotypes

A new bHLH gene from mouse that we call pMesogenin1 (referring to paraxial mesoderm-specific expression and regulatory capacities) and its candidate o rtholog from Xenopus were isolated and studied comparatively, Tn both organ isms the gene is specifically expressed in unsegmented paraxial mesoderm an d its immediate progenitors. A striking feature of pMesogenin1 expression i s that it terminates abruptly in presumptive somites (somitomeres). Somitom eres rostral to the pMesogenin1 domain strongly upregulate expression of pM esogenin's closest known paralogs, MesP1 and MesP2 (Thylacine1/2 in Xenopus ), Subsequently, the most rostral somitomere becomes a new somite and expre ssion of MesP1/2 is sharply downregulated before this transition. Thus, exp ression patterns of these bHLH genes, together with that of an additional b HLH gene in the mouse, Paraxis, collectively define discrete but highly dyn amic prepatterned subdomains of the paraxial mesoderm, In functional assays , we show that pMesogenin1 from either mouse or frog can efficiently drive nonmesodermal cells to assume a phenotype with molecular and cellular chara cteristics of early paraxial mesoderm, Among genes induced by added pMesoge nin1 is Xwnt-8, a signaling factor that induces a similar repertoire of mar ker genes and a similar cellular phenotype, Additional target genes Induced by pMesogenin1 are ESR4/5, regulators known to play a significant role in segmentation of paraxial mesoderm (W. C. Jen et al., 1999, Genes Dev. 13, 1 486-1449). pMesogenin1 differs from other known mesoderm-inducing transcrip tion factors because it does not also activate a dorsal (future axial) meso derm phenotype, suggesting that pMesogenin1 is involved in specifying parax ial mesoderm. In the context of the intact hog embryo, ectopic pMesogenin1 also actively suppressed axial mesoderm markers and disrupted normal format ion of notochord. In addition, we found evidence for cross-regulatory inter actions between pMesogenin1 and T-box transcription factors, a family of ge nes normally expressed in a broader pattern and known to induce multiple ty pes of mesoderm. Based on our results and results from prior studies of rel ated bHLH genes, we propose that pMesogenin1 and its closest known relative s, MesP1/2 (in mouse) and Thylacine1/2 (in Xenopus), comprise a bHLH subfam ily devoted to formation and segmentation of paraxial mesoderm. (C) 2000 Ac ademic Press.