Tcf7l1 proteins cell autonomously restrict cardiomyocyte and promote endothelial specification in zebrafish.
Tcf7l1 proteins cell autonomously restrict cardiomyocyte and promote endothelial specification in zebrafish.
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DOI：
10.1016/j.ydbio.2013.05.016
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发表时间：
2013-08-15
影响因子：
2.7
通讯作者：
Waxman JS
中科院分区：
文献类型：
--
作者：
Sorrell MR;Dohn TE;D'Aniello E;Waxman JS
Tcf7l1（以前称为 Tcf3）蛋白是保守的转录因子，其作为转录抑制因子的功能通过与 β-连环蛋白的相互作用而得到缓解。尽管 Tcf7l1 蛋白的功能已在许多发育环境中进行了研究，但这种保守的 Wnt 信号传导介质是否是适当的心肌细胞 (CM) 发育所必需的尚未得到研究。我们发现 Tcf7l1 蛋白在两个发育时期是限制斑马鱼胚胎中 CM 数量所必需的：原肠胚形成之前和 CM 分化的初始波之后。与前神经模式形成中部分冗余的作用相反，我们发现 Tcf7l1a 和 Tcf7l1b 在前中胚层模式形成期间限制 CM 规范方面具有非冗余功能，这表明在两个斑马鱼 Tcf7l1 旁系同源物之间，早期 CM 规范期间提供的转录抑制存在限制。通过细胞移植实验，我们确定 Tcf7l1 旁系同源物是细胞自主限制 CM 规范并促进内皮细胞 (EC) 规范所必需的，这与 Wnt 信号传导指导胚胎干细胞中这些祖细胞之间转化的能力明显相似。因此，这些结果表明，在中胚层的前后模式形成过程中，Tcf7l1 蛋白是细胞自主地需要限制 Wnt 信号传导，从而平衡前侧板中胚层内的 CM 和 EC 祖细胞规范。这项研究扩展了我们对 Tcf7l1 蛋白体内发育需求以及脊椎动物 CM 发育的机制的理解。
Tcf7l1 (formerly Tcf3) proteins are conserved transcription factors whose function as transcriptional repressors is relieved through interactions with β-catenin. Although the functions of Tcf7l1 proteins have been studied in many developmental contexts, whether this conserved mediator of Wnt signaling is required for appropriate cardiomyocyte (CM) development has not been investigated. We find that Tcf7l1 proteins are necessary during two developmental periods to limit CM number in zebrafish embryos: prior to gastrulation and after the initial wave of CM differentiation. In contrast to partially redundant roles in anterior neural patterning, we find that Tcf7l1a and Tcf7l1b have non-redundant functions with respect to restricting CM specification during anterior mesodermal patterning, suggesting that between the two zebrafish Tcf7l1 paralogs there is a limit to the transcriptional repression provided during early CM specification. Using cell transplantation experiments, we determine that the Tcf7l1 paralogs are required cell autonomously to restrict CM specification and promote endothelial cell (EC) specification, which is overtly similar to the ability of Wnt signaling to direct a transformation between these progenitors in embryonic stem cells. Therefore, these results argue that during anterior-posterior patterning of the mesoderm Tcf7l1 proteins are cell autonomously required to limit Wnt signaling, which balances CM and EC progenitor specification within the anterior lateral plate mesoderm. This study expands our understanding of the in vivo developmental requirements of Tcf7l1 proteins and the mechanisms directing CM development in vertebrates.
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