PDF(Pubmed)
Abstract：
Ventricular and atrial cardiac chambers have unique structural and contractile characteristics that underlie their distinct functions. The maintenance of chamber-specific features requires active reinforcement, even in differentiated cardiomyocytes. Previous studies in zebrafish have shown that sustained FGF signaling acts upstream of Nkx factors to maintain ventricular identity, but the rest of this maintenance pathway remains unclear. Here, we show that MEK1/2-ERK1/2 signaling acts downstream of FGF and upstream of Nkx factors to promote ventricular maintenance. Inhibition of MEK signaling, like inhibition of FGF signaling, results in ectopic atrial gene expression and reduced ventricular gene expression in ventricular cardiomyocytes. FGF and MEK signaling both influence ventricular maintenance over a similar timeframe, when phosphorylated ERK (pERK) is present in the myocardium. However, the role of FGF-MEK activity appears to be context-dependent: some ventricular regions are more sensitive than others to inhibition of FGF-MEK signaling. Additionally, in the atrium, although endogenous pERK does not induce ventricular traits, heightened MEK signaling can provoke ectopic ventricular gene expression. Together, our data reveal chamber-specific roles of MEK-ERK signaling in the maintenance of ventricular and atrial identities.
摘要：
心室和心房心腔具有独特的结构和收缩特征，这是其独特功能的基础。腔室特定特征的维护需要主动加固，甚至在分化的心肌细胞中。先前在斑马鱼中的研究表明，持续的FGF信号在Nkx因子的上游起作用，以维持心室同一性，但这种维持途径的其余部分仍不清楚。这里,我们发现MEK1/2-ERK1/2信号传导作用于FGF下游和Nkx因子上游,促进心室维持.MEK信号的抑制，类似FGF信号的抑制，结果在心室心肌细胞中异位心房基因表达和心室基因表达降低。FGF和MEK信号在相似的时间范围内都会影响心室维持，当磷酸化ERK（pERK）存在于心肌中时。然而,FGF-MEK活性的作用似乎与背景相关:一些心室区域对FGF-MEK信号传导的抑制比其他区域更敏感.此外,在中庭，虽然内源性pERK不诱导心室特性，增强的MEK信号可以引起异位心室基因表达。一起,我们的数据揭示了MEK-ERK信号传导在维持心室和心房特性中的腔室特异性作用.
