Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation.
Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation.
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DOI：
10.1002/stem.1674
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发表时间：
2014-06
期刊：
影响因子：
5.2
通讯作者：
Meech, Robyn
中科院分区：
文献类型：
--
作者：
Zhuang, Lizhe;Hulin, Julie-Ann;Gromova, Anastasia;Thi Diem Tran Nguyen;Yu, Ruth T.;Liddle, Christopher;Downes, Michael;Evans, Ronald M.;Makarenkova, Helen P.;Meech, Robyn
经典的Wnt信号通路对于肌发生是至关重要的，并且可以诱导肌肉祖细胞从增殖切换到分化; Wnt信号如何在这个过程中与肌肉特异性调节因子整合知之甚少。我们以前证明了Barx 2同源框蛋白与肌肉调节因子（MRF）MyoD合作促进分化。Pax 7是另一个重要的肌肉同源盒因子，抑制分化。我们现在确定Barx 2，MyoD和Pax 7作为Wnt效应复合物的新组分，为调节肌肉祖细胞分化提供了新的分子途径。经典Wnt信号转导诱导肌肉祖细胞中的Barx 2表达，并且Barx 2的扰动导致Wnt靶基因的误调节。Barx 2激活两个内源性Wnt靶启动子以及Wnt报告基因TOPflash，后者与MyoD协同作用。此外，Barx 2与核心Wnt效应子β-连环蛋白和TCF相互作用，被募集到TCF/LEF位点，并促进β-连环蛋白的募集。相反，Pax 7抑制Wnt报告基因并拮抗Barx 2的激活作用。Pax 7也结合β-连环蛋白，表明Barx 2和Pax 7可能竞争与核心Wnt效应复合物的相互作用。总的来说，数据首次表明Barx 2，Pax 7和MRF可以作为成肌细胞中Wnt信号的直接转录效应子，并且Barx 2和Wnt信号传导参与调控环。我们认为Barx 2和Pax 7在Wnt信号调节中的拮抗作用可能有助于介导成肌细胞从增殖到分化的转变。
The canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2, MyoD, and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors β-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of β-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds β-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation.
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影响因子：
11.4
作者：
Hecht, A;Vleminckx, K;Kemler, R
通讯作者：
Kemler, R
影响因子：
4.6
作者：
Lepper, Christoph;Partridge, Terence A.;Fan, Chen-Ming
通讯作者：
Fan, Chen-Ming
影响因子：
2.7
作者：
Abu-Elmagd, Muhammad;Robson, Lesley;Munsterberg, Andrea
通讯作者：
Munsterberg, Andrea
影响因子：
4.6
作者：
McCarthy, John J.;Mula, Jyothi;Peterson, Charlotte A.
通讯作者：
Peterson, Charlotte A.
影响因子：
8
作者：
Attema, J. L.;Pronk, C. J. H.;Bryder, D.
通讯作者：
Bryder, D.