尽管众多信号通路已被确定对心脏再生和修复过程具有促进作用，但对抑制损伤诱导的心肌细胞去分化和增殖的分子途径和机制尚不清楚。我们近期研究工作发现，Gridlock(Grl)/Hey2转录因子在受损成年斑马鱼心脏中表达下调；而且，Grl/Hey2在心肌层过表达抑制心肌细胞增殖和心脏再生。研究心脏修复与再生过程中阻止心肌细胞增殖的调节因子和分子屏障是再生领域中的一个关键科学问题。本课题拟在前期工作基础上，应用条件性过表达和基因敲除技术研究Grl/Hey2对成年斑马鱼心脏再生与修复的负调节作用机制，探讨Grl/Hey2在成年心脏稳态维持中的影响和作用。最后，我们还将发现在心脏再生过程中依赖于Grl/Hey2转录活性的下游作用因子，并探索这些因子如何影响Grl/Hey2调控心脏修复和再生过程。我们的研究不仅有助于了解抑制损伤诱导的心肌细胞去分化和增殖的分子机制，还将为心脏疾病的治疗提供新策略。

Various signaling pathways have been identified to initiate and achieve heart repair and regeneration. However, the molecular pathways and mechanisms that prevent injury-induced cardiomyocyte (CM) dedifferentiation and proliferation are incompletely understood. Our recent study reveals that Gridlock (Grl)/Hey2 expression is reduced in adult zebrafish heart following cardiac injury. Importantly, myocardial Grl/Hey2 overexpression inhibits CM proliferation and heart regeneration. Understanding molecular regulators and roadblocks that prevent CMs from entering proliferation during regeneration is a key question in the field. In this project, we aim to investigate the negative control mechanism of Grl/Hey2 during zebrafish heart repair and regeneration, and study the roles of Grl/Hey2 in regulating cardiac homeostasis, using conditional overexpression and CRISPR/Cas9-mediated knockout techniques. We will also identify Grl/Hey2-mediated downstream factors during injury-induced heart repair and regeneration, and further explore how these downstream factors influence Grl/Hey2 to regulate heart regeneration and repair. Our research will not only help to understand the mechanisms whereby the molecular barriers prevent injury-induced CM dedifferentiation and proliferation, but may also provide new strategies for treatment of cardiovascular diseases.