The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field
The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field
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DOI：
10.1242/dev.126136
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发表时间：
2016-01-01
期刊：
影响因子：
4.6
通讯作者：
Burns, C. Geoffrey
中科院分区：
文献类型：
--
作者：
Jahangiri, Leila;Sharpe, Michka;Burns, C. Geoffrey
脊椎动物的心脏是通过心肌细胞分化的连续阶段形成的。最初，来自第一心区(FHF)前体细胞的心肌细胞组装成线性心管。此后，第二心域(SHF)前体细胞分化为心肌细胞，这些细胞在明确的发育窗口内附着在心管的两极。虽然心管延长缺陷会导致危及生命的先天性心脏缺陷，但控制心肌肥大的起始、速度和持续时间的变量仍然不清楚。在这里，我们证明了AP-1转录因子，Fos-like抗原2(Fosl2)，增强了斑马鱼SHF的心肌增生速度。Fosl2突变体适当地启动了增殖，但心肌细胞的产生迟缓，导致了心室功能缺陷和SHF前体细胞的积累。令人惊讶的是，突变胚胎最终通过延长积累窗口来纠正心肌缺陷。Fosl2的过度表达也影响了SHF来源的心室肌细胞的产生，这一表型与祖细胞池的早衰一致。我们的数据表明，Fosl2促进了祖细胞向心肌细胞的转变，并揭示了存在调节机制，以确保SHF介导的心肌细胞贡献与胚胎时期无关。
The vertebrate heart forms through successive phases of cardiomyocyte differentiation. Initially, cardiomyocytes derived from first heart field (FHF) progenitors assemble the linear heart tube. Thereafter, second heart field (SHF) progenitors differentiate into cardiomyocytes that are accreted to the poles of the heart tube over a well-defined developmental window. Although heart tube elongation deficiencies lead to life-threatening congenital heart defects, the variables controlling the initiation, rate and duration of myocardial accretion remain obscure. Here, we demonstrate that the AP-1 transcription factor, Fos-like antigen 2 (Fosl2), potentiates the rate of myocardial accretion from the zebrafish SHF. fosl2 mutants initiate accretion appropriately, but cardiomyocyte production is sluggish, resulting in a ventricular deficit coupled with an accumulation of SHF progenitors. Surprisingly, mutant embryos eventually correct the myocardial deficit by extending the accretion window. Overexpression of Fosl2 also compromises production of SHF-derived ventricular cardiomyocytes, a phenotype that is consistent with precocious depletion of the progenitor pool. Our data implicate Fosl2 in promoting the progenitor to cardiomyocyte transition and uncover the existence of regulatory mechanisms to ensure appropriate SHF-mediated cardiomyocyte contribution irrespective of embryonic stage.