Subfunctionalization and neofunctionalization of vertebrate Lef/Tcf transcription factors
Subfunctionalization and neofunctionalization of vertebrate Lef/Tcf transcription factors
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DOI：
10.1016/j.ydbio.2012.05.012
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发表时间：
2012-08-01
影响因子：
2.7
通讯作者：
Gradl, Dietmar
中科院分区：
文献类型：
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作者：
Klingel, Susanne;Morath, Iris;Gradl, Dietmar
无脊椎动物表达多种Wnt配体，并且所有Wnt/β-连环蛋白信号传导途径都会聚到仅一个核Lef/Tcf。然而，在脊椎动物中，四种不同的Lef/Tcfs，即Tcf-1，Lef，Tcf-3和Tcf-4履行这一功能。目前，在脊椎动物中，各种Lef/Tcfs在功能上相似或多样化的程度在很大程度上是未知的。具体而言，尚不知道哪些结构域负责Tcf亚型特异性功能。我们研究了保守和非保守的功能的各种Tcfs，通过使用非洲爪蟾作为模式生物和测试Tcfs从水螅magnipripiata，秀丽隐杆线虫和果蝇。为了鉴定与个体性质相关的结构域，我们创建了一系列由XTcf-3的部分组成的嵌合构建体。XTcf-1和HyTcf.在非洲爪蟾变形的救援实验表明，测试的三种无脊椎动物Tcfs补偿了不同非洲爪蟾Tcfs的损失：果蝇Tcf（穿山甲）可以替代XTcf-1，XTcf-3和XTcf-4的损失。相比之下，小杆线虫Tcf（Pop-1）和水螅Tcf（HyTcf）可以分别替代仅XTcf-3和XTcf-4的损失。负责亚型特异性功能的结构域是调节性CRD结构域。系统发育分析将Tcf-1/Lef-1与脊椎动物谱系中的姐妹组Tcf-3/4分开。我们建议，脊椎动物特定的多样化的Tcfs在脊椎动物中导致亚功能化的Tcf已经团结的大部分的Lef/Tcf功能。(C)2012 Elsevier Inc. All rights reserved.
Invertebrates express a multitude of Wnt ligands and all Wnt/beta-catenin signaling pathways converge to only one nuclear Lef/Tcf. In vertebrates, however, four distinct Lef/Tcfs, i.e. Tcf-1, Lef, Tcf-3, and Tcf-4 fulfill this function. At present, it is largely unknown to what extent the various Lef/Tcfs are functionally similar or diversified in vertebrates. In particular, it is not known which domains are responsible for the Tcf subtype specific functions. We investigated the conserved and non-conserved functions of the various Tcfs by using Xenopus laevis as a model organism and testing Tcfs from Hydra magnipapillata, Caenorhabditis elegans and Drosophila melanogaster. In order to identify domains relevant for the individual properties we created series of chimeric constructs consisting of parts of XTcf-3. XTcf-1 and HyTcf. Rescue experiments in Xenopus morphants revealed that the three invertebrate Tcfs tested compensated the loss of distinct Xenopus Tcfs: Drosophila Tcf (Pangolin) can substitute for the loss of XTcf-1, XTcf-3 and XTcf-4. By comparison, Caenorhabditis Tcf (Pop-1) and Hydra Tcf (HyTcf) can substitute for the loss of only XTcf-3 and XTcf-4, respectively. The domain, which is responsible for subtype specific functions is the regulatory CRD domain. A phylogenetic analysis separates Tcf-1/Lef-1 from the sister group Tcf-3/4 in the vertebrate lineage. We propose that the vertebrate specific diversification of Tcfs in vertebrates resulted in subfunctionalization of a Tcf that already united most of the Lef/Tcf functions. (C) 2012 Elsevier Inc. All rights reserved.