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Integrin α5 and Integrin α4 cooperate to promote endocardial differentiation and heart morphogenesis.
Developmental Biology ( IF 2.7 ) Pub Date : 2020-07-03 , DOI: 10.1016/j.ydbio.2020.06.006
Jennifer A Schumacher 1 , Zoë A Wright 2 , Mackenzie L Owen 2 , Nina O Bredemeier 2 , Saulius Sumanas 3
Affiliation  

Endocardium is critically important for proper function of the cardiovascular system. Not only does endocardium connect the heart to blood vasculature, it also plays an important role in heart morphogenesis, valve formation, and ventricular trabeculation. The extracellular protein Fibronectin (Fn1) promotes endocardial differentiation, but the signaling pathways downstream of Fn1 that regulate endocardial development are not understood. Here, we analyzed the role of the Fibronectin receptors Integrin alpha5 (Itga5) and Integrin alpha4 (Itga4) in zebrafish heart development. We show that itga5 mRNA is expressed in both endocardium and myocardium during early stages of heart development. Through analysis of both itga5 single mutants and itga4;itga5 double mutants, we show that loss of both itga5 and itga4 results in enhanced defects in endocardial differentiation and morphogenesis compared to loss of itga5 alone. Loss of both itga5 and itga4 results in cardia bifida and severe myocardial morphology defects. Finally, we find that loss of itga5 and itga4 results in abnormally narrow anterior endodermal sheet morphology. Together, our results support a model in which Itga5 and Itga4 cooperate to promote endocardial differentiation, medial migration of endocardial and myocardial cells, and morphogenesis of anterior endoderm.



中文翻译:

整合素α5和整合素α4共同促进心内膜分化和心脏形态发生。

心内膜对于心血管系统的正常功能至关重要。心内膜不仅将心脏连接到血管系统,而且还在心脏形态发生,瓣膜形成和心室小梁形成中起重要作用。细胞外蛋白纤连蛋白(Fn1)促进心内膜分化,但尚不清楚调节心内膜发育的Fn1下游信号通路。在这里,我们分析了纤连蛋白受体整合素α5(Itga5)和整合素α4(Itga4)在斑马鱼心脏发育中的作用。我们显示,itga5 mRNA在心脏发育的早期在心内膜和心肌中均表达。通过分析itga5单突变体和itga4; itga5与双突变体相比,我们发现itga5itga4的缺失与单独itga5的缺失相比,会导致心内膜分化和形态发生的缺陷增加。itga5itga4的缺失都会导致card门裂和严重的心肌形态缺陷。最后,我们发现itga5itga4的缺失导致异常狭窄的前内膜片形态。在一起,我们的结果支持其中Itga5和Itga4协同作用以促进心内膜分化,心内膜和心肌细胞的内侧迁移以及前内胚层形态发生的模型。

更新日期:2020-07-20
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