School of Life Sciences, Fudan University, Shanghai 200438, China.
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Int J Mol Sci. 2021 Apr 11;22(8):3945. doi: 10.3390/ijms22083945.
Cardiac regenerative capacity varies widely among vertebrates. Zebrafish can robustly regenerate injured hearts and are excellent models to study the mechanisms of heart regeneration. Recent studies have shown that enhancers are able to respond to injury and regulate the regeneration process. However, the mechanisms to activate these regeneration-responsive enhancers (RREs) remain poorly understood. Here, we utilized transient and transgenic analysis combined with a larval zebrafish ventricle ablation model to explore the activation and regulation of a representative RRE. -linked enhancer sequence () directed enhanced green fluorescent protein (EGFP) expression in response to larval ventricle regeneration and such activation was attenuated by hemodynamic force alteration and mechanosensation pathway modulation. Further analysis revealed that Notch signaling influenced the endocardial activity as well as endogenous expression. Altogether, our work has established zebrafish models for rapid characterization of cardiac RREs in vivo and provides novel insights on the regulation of by hemodynamic forces and other signaling pathways during heart regeneration.
脊椎动物的心脏再生能力差异很大。斑马鱼能够强烈地再生受损的心脏，是研究心脏再生机制的优秀模型。最近的研究表明，增强子能够对损伤做出反应，并调节再生过程。然而，激活这些再生反应增强子（RREs）的机制仍知之甚少。在这里，我们利用瞬时和转基因分析，结合幼鱼斑马鱼心室消融模型，探索了一个代表性 RRE 的激活和调控。与 连接的增强子序列（）指导增强型绿色荧光蛋白（EGFP）的表达，以响应幼鱼心室再生，这种激活被血液动力学力改变和机械感觉途径调节所减弱。进一步的分析表明，Notch 信号影响心内膜的活性以及内源性的表达。总的来说，我们的工作建立了斑马鱼模型，用于快速体内表征心脏 RREs，并为心脏再生过程中血液动力学力和其他信号通路对的调节提供了新的见解。
