Pbx4 is Required for the Temporal Onset of Zebrafish Myocardial Differentiation.
Pbx4 is Required for the Temporal Onset of Zebrafish Myocardial Differentiation.
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DOI：
10.3390/jdb3040093
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发表时间：
2015
影响因子：
2.7
通讯作者：
Maves L
中科院分区：
文献类型：
--
作者：
Kao RM;Rurik JG;Farr GH 3rd;Dong XR;Majesky MW;Maves L
适当控制细胞分化的时间开始对于调节细胞谱系决定和发育过程中的形态发生至关重要。Pbx同源域转录因子已成为细胞分化的重要调控因子。我们之前通过反义morpholino敲低表明，Pbx因子是斑马鱼心肌分化及时激活所必需的。为了进一步了解Pbx因子在心脏发育中的作用，我们在这里展示了斑马鱼pbx4突变胚胎心肌分化的延迟发生，例如前外侧板中胚层早期心肌细胞tnnt2a表达的延迟激活。我们还观察到延迟的心肌形态发生和心室和心房的畸形模式，与我们之前的Pbx敲除研究一致。此外，我们发现pbx4突变体幼虫有异常的流出道和心外膜前标记tbx18的表达缺陷。最后，我们提出了Pbx在心肌细胞前体中表达的证据，以及在发育中的心室附近表达泛细胞角蛋白的心外膜前细胞中异质Pbx表达的证据。总之，我们的数据表明，Pbx4是心肌分化的适当时间激活所必需的，并为研究Pbx因子在心脏发育中的其他作用奠定了基础。
Proper control of the temporal onset of cellular differentiation is critical for regulating cell lineage decisions and morphogenesis during development. Pbx homeodomain transcription factors have emerged as important regulators of cellular differentiation. We previously showed, by using antisense morpholino knockdown, that Pbx factors are needed for the timely activation of myocardial differentiation in zebrafish. In order to gain further insight into the roles of Pbx factors in heart development, we show here that zebrafish pbx4 mutant embryos exhibit delayed onset of myocardial differentiation, such as delayed activation of tnnt2a expression in early cardiomyocytes in the anterior lateral plate mesoderm. We also observe delayed myocardial morphogenesis and dysmorphic patterning of the ventricle and atrium, consistent with our previous Pbx knock-down studies. In addition, we find that pbx4 mutant larvae have aberrant outflow tracts and defective expression of the proepicardial marker tbx18. Finally, we present evidence for Pbx expression in cardiomyocyte precursors as well as heterogeneous Pbx expression among the pan-cytokeratin-expressing proepicardial cells near the developing ventricle. In summary, our data show that Pbx4 is required for the proper temporal activation of myocardial differentiation and establish a basis for studying additional roles of Pbx factors in heart development.