The evolutionally conserved activity of Dapper2 in antagonizing TGF-β signaling
The evolutionally conserved activity of Dapper2 in antagonizing TGF-β signaling
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DOI：
10.1096/fj.06-6246com
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Ye-Guang
中科院分区：
文献类型：
--
作者：
Su, Ying;Zhang, Long;Chen, Ye-Guang
作为Dapper家族的两个不同成员，Dapper1和Dapper2被认为可以调节非洲爪鱼和斑马鱼的Wnt和tgf - β /节点信号。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Dapper2的小鼠同源基因mDpr2，并研究了其在调节tgf - β信号活性中的功能。在这里，我们发现，与斑马鱼Dapper2一样，mDpr2的过表达抑制了tgf - β诱导的smad应答报告蛋白的表达，并在哺乳动物细胞中靶向tgf - β I型受体ALK5进行降解。mBpr2在斑马鱼胚胎中的过表达导致中胚层标记物no tail和goosecoid在屏蔽期和眼融合后期的表达降低，这意味着mDpr2可能具有与鱼类Dapper2相似的内在体内活性。mDpr2在小鼠胚胎中原肠胚形成前后的整个外胚层以及后期的体、神经管和肠道中都有表达，这意味着在早期胚胎发育中起作用。我们的数据表明，Dpr2作为tgf - β /节点信号通路的负调节因子的功能在进化上是保守的，至少部分是在鱼类和哺乳动物中保守的。
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 mBpr2 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.