The evolutionally conserved activity of Dapper2 in antagonizing TGF-beta signaling.
The evolutionally conserved activity of Dapper2 in antagonizing TGF-beta signaling.
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发表时间：
2007
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通讯作者：
Ying Su;Long Zhang;Xia Gao;Fanwei Meng;Jun Wen;Hu Zhou;A. Meng;Ye-Guang Chen
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作者：
Ying Su;Long Zhang;Xia Gao;Fanwei Meng;Jun Wen;Hu Zhou;A. Meng;Ye-Guang Chen
Dapper 1和Dapper 2是Dapper家族的两个不同成员，已被认为调节爪蟾和斑马鱼中的Wnt和TGF-β/Nodal信号传导。为了更好地了解Dapper在哺乳动物中的功能，我们克隆了斑马鱼Dapper 2的小鼠直系同源物mDpr 2，并研究了其在调节TGF-β信号传导活性中的功能。在这里，我们发现，像斑马鱼Dapper 2，mDpr 2的过表达抑制TGF-β诱导的Smad反应性报告基因的表达，并靶向TGF-β I型受体ALK 5在哺乳动物细胞中降解。在斑马鱼胚胎中过表达mDpr 2导致中胚层标记物no tail和goosecoid在盾状期和眼融合期后的表达减少，这意味着mDpr 2可能具有与鱼类Dapper 2活性相似的内在体内活性。在小鼠胚胎中，在原肠胚形成开始时的整个上胚层和体节、神经管和肠中检测到mDpr 2的表达，这意味着在早期胚胎发育中的作用。我们的数据表明，Dpr 2作为TGF-β/Nodal信号通路的负调节因子的功能在鱼类和哺乳动物中至少部分是进化保守的。
Dapper1 and Dapper2, two divergent members of the Dapper family, have been suggested to modulate Wnt and TGF-beta/Nodal signaling in Xenopus and zebrafish. To get a better understanding of Dapper function in mammals, we have cloned the mouse ortholog of zebrafish Dapper2, mDpr2 and investigated its function in regulating TGF-beta signaling activity. Here, we showed that, like zebrafish Dapper2, overexpression of mDpr2 inhibited the TGF-beta-induced expression of the Smad-responsive reporters and targeted TGF-beta type I receptor ALK5 for degradation in mammalian cells. Overexpression of mDpr2 in the zebrafish embryos led to a decrease in expression of the mesoderm marker no tail and goosecoid at the shield stage and eye fusion later, implying that mDpr2 may have an intrinsic in vivo activity similar to fish Dapper2 activity. The expression of mDpr2 was detected throughout the epiblast around the onset of gastrulation and in somites, the neural tube and gut at later stages in mouse embryos, implying a role in early embryonic development. Our data indicate that the function of Dpr2 as a negative regulator of the TGF-beta/Nodal signal pathway is evolutionally conserved, at least in part, in fish and mammals.