Pogoda Hans-Martin, Meyer Dirk
Department of Developmental Biology, Biology I, University of Freiburg, Freiburg, Germany.
Dev Dyn. 2002 Jul;224(3):334-49. doi: 10.1002/dvdy.10113.
Growth factors of the TGF-beta superfamily such as BMPs and Nodals are important signaling factors during all stages of animal development. Smad proteins, the cytoplasmic mediators of most TGF-beta signals in vertebrates, play central roles not only for transmission but also in controlling inductive TGF-beta signals by feedback regulation. Here, we describe cloning, expression pattern, transcriptional regulation, and functional properties of two novel zebrafish Smad proteins: the TGF-beta agonist Smad3b, and the anti-Smad Smad7. We show that zebrafish Smad3b, in contrast to the related zebrafish Smad2, can induce mesoderm independently of TGF-beta signaling. Although mammalian Smad3 was shown to inhibit expression of the organizer-specific genes goosecoid, zebrafish smad3b activates organizer genes such as goosecoid. Furthermore, we show that Smad3 and BMP signals activate smad7. Because Smad7 blocks distinct TGF-beta signals in early zebrafish development, our data provide hints for new roles of smad3 genes in the regulation and modulation of TGF-beta signals. In summary, our analyses point out differences of Smad3b and Smad2 functions in zebrafish and provide the first link of smad3 and smad7 function in context of vertebrate development.
转化生长因子-β（TGF-β）超家族的生长因子，如骨形态发生蛋白（BMPs）和Nodal，在动物发育的所有阶段都是重要的信号因子。Smad蛋白是脊椎动物中大多数TGF-β信号的细胞质介质，不仅在信号传递中起核心作用，还通过反馈调节控制诱导性TGF-β信号。在此，我们描述了两种新型斑马鱼Smad蛋白的克隆、表达模式、转录调控和功能特性：TGF-β激动剂Smad3b和抗Smad蛋白Smad7。我们发现，与相关的斑马鱼Smad2不同，斑马鱼Smad3b可独立于TGF-β信号诱导中胚层形成。虽然哺乳动物Smad3被证明可抑制组织者特异性基因goosecoid的表达，但斑马鱼smad3b可激活诸如goosecoid等组织者基因。此外，我们发现Smad3和BMP信号可激活smad7。由于Smad7在斑马鱼早期发育中可阻断不同的TGF-β信号，我们的数据为smad3基因在TGF-β信号调控和调节中的新作用提供了线索。总之，我们的分析指出了斑马鱼中Smad3b和Smad2功能的差异，并在脊椎动物发育背景下首次建立了smad3和smad7功能之间的联系。
