Tbx20 drives cardiac progenitor formation and cardiomyocyte proliferation in zebrafish.
Tbx20 drives cardiac progenitor formation and cardiomyocyte proliferation in zebrafish.
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DOI：
10.1016/j.ydbio.2016.12.009
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发表时间：
2017-01-15
影响因子：
2.7
通讯作者：
Chen JN
中科院分区：
文献类型：
--
作者：
Lu F;Langenbacher A;Chen JN
Tbx 20是一种T-box转录因子，在心脏的发育和维持中起重要作用。虽然它是由心脏祖细胞在所有物种的研究，参与Tbx 20在脊椎动物的心脏祖细胞形成之前没有被描述。在这里，我们报告的鉴定斑马鱼tbx 20突变，导致在一个无活性的，截短的蛋白质缺乏任何功能域。在这种突变体中，心脏祖细胞数量大大减少，导致形成一个小的、伸展的心脏。我们发现，Tbx 20的过度表达导致心脏扩大，心肌细胞明显增多。有趣的是，这种细胞数量的增加是由增强的心脏祖细胞形成和分化的心肌细胞的增殖引起的，并且依赖于Tbx 20的T-box和转录激活结构域的活性。总之，我们的研究结果突出了Tbx 20在促进脊椎动物心脏祖细胞形成中的先前未被重视的作用，并揭示了其激活结构域在胚胎发生期间心脏细胞增殖中的新功能。
Tbx20 is a T-box transcription factor that plays essential roles in the development and maintenance of the heart. Although it is expressed by cardiac progenitors in all species examined, an involvement of Tbx20 in cardiac progenitor formation in vertebrates has not been previously described. Here we report the identification of a zebrafish tbx20 mutation that results in an inactive, truncated protein lacking any functional domains. The cardiac progenitor population is strongly diminished in this mutant, leading to the formation of a small, stretched-out heart. We found that overexpression of Tbx20 results in an enlarged heart with significantly more cardiomyocytes. Interestingly, this increase in cell number is caused by both enhanced cardiac progenitor cell formation and the proliferation of differentiated cardiomyocytes, and is dependent upon the activity of Tbx20’s T-box and transcription activation domains. Together, our findings highlight a previously unappreciated role for Tbx20 in promoting cardiac progenitor formation in vertebrates and reveal a novel function for its activation domain in cardiac cell proliferation during embryogenesis.