Schmidt M, Tanaka M, Münsterberg A
Division of Cell and Developmental Biology, Department of Anatomy and Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Development. 2000 Oct;127(19):4105-13. doi: 10.1242/dev.127.19.4105.
The developmental signals that govern cell specification and differentiation in vertebrate somites are well understood. However, little is known about the downstream signalling pathways involved. We have shown previously that a combination of Shh protein and Wnt1 or Wnt3a-expressing fibroblasts is sufficient to activate skeletal muscle-specific gene expression in somite explants. Here, we have examined the molecular mechanisms by which the Wnt-mediated signal acts on myogenic precursor cells. We show that chick frizzled 1 (Fz1), beta-catenin and Lef1 are expressed during somitogenesis. Lef1 and beta-catenin transcripts become restricted to the developing myotome. Furthermore, beta-catenin is expressed prior to the time at which MyoD transcripts can be detected. Expression of beta-catenin mRNA is regulated by positive and negative signals derived from neural tube, notochord and lateral plate mesoderm. These signals include Bmp4, Shh and Wnt1/Wnt3a itself. In somite explants, Fz1, beta-catenin and Lef1 are expressed prior to activation of myogenesis in response to Shh and Wnt signals. Thus, our data show that a combination of Shh and Wnt1 upregulates expression of Wnt pathway components in developing somites prior to myogenesis. Thus, Wnt1 could act through beta-catenin on cells in the myotome.
调控脊椎动物体节中细胞特化和分化的发育信号已为人熟知。然而,对于所涉及的下游信号通路却知之甚少。我们之前已经表明,Shh蛋白与表达Wnt1或Wnt3a的成纤维细胞的组合足以激活体节外植体中骨骼肌特异性基因的表达。在此,我们研究了Wnt介导的信号作用于成肌前体细胞的分子机制。我们发现鸡卷曲蛋白1(Fz1)、β-连环蛋白和淋巴样增强因子1(Lef1)在体节发生过程中表达。Lef1和β-连环蛋白转录本局限于发育中的肌节。此外,β-连环蛋白在可检测到MyoD转录本之前就已表达。β-连环蛋白mRNA的表达受来自神经管、脊索和侧板中胚层的正负信号调控。这些信号包括骨形态发生蛋白4(Bmp4)、Shh和Wnt1/Wnt3a自身。在体节外植体中,Fz1、β-连环蛋白和Lef1在响应Shh和Wnt信号激活成肌作用之前就已表达。因此,我们的数据表明,在成肌作用之前,Shh和Wnt1的组合上调了发育中体节中Wnt信号通路成分的表达。因此,Wnt1可能通过β-连环蛋白作用于肌节中的细胞。