GENETIC DISSECTION OF MICRORNA FUNCTION DURING HEART REGENERATION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 哺乳动物的心脏对急性心肌梗死的反应是形成富含胶原的疤痕组织。相比之下，斑马鱼的心脏将经历心肌细胞(CM)的增殖，以修复受损或缺失的心肌壁部分，从而使心脏功能完全恢复。为什么某些生物能够更好地再生丢失和受损的组织，这是三个多世纪以来密集研究的主题。然而到目前为止，我们对刺激器官再生的遗传学知之甚少。然而，很明显，从分化的组织转变为高度增殖和再生的细胞需要在发育程序上做出巨大的改变。在这项提案中，我将通过重点研究关键处理酶DICER和两个特定的miRNAs，miR-21和miR133的作用，来研究microRNAs(MiRNAs)作为心脏再生过程中遗传程序变化的调节器的作用。在我的研究中，我将使用强大的脊椎动物斑马鱼作为遗传模型系统，因为它具有强大的心脏再生能力。我这项研究的目标是通过使用可诱导的改变miRNA活性的转基因菌株来确定组织特异性miRNA是如何调控心脏再生的。我的研究将加强潜在的治疗方法，以增加成人心脏的存活和再生 缺血损伤后的肌肉。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In response to an acute myocardial infarction, the mammalian heart responds with formation of collagen-laden scar tissue. In contrast, the zebrafish heart will undergo cardiomyocyte (CM) proliferation to repair the damaged or missing portion of the myocardial wall, thereby enabling complete restoration of cardiac function. Why certain organisms are better equipped to regenerate lost and damaged tissue has been the subject of intense studies for over three centuries. Yet to date, we know very little about the genetics that stimulate organ regeneration. It is clear however, that the transformation from a differentiated tissue into highly proliferative and regenerative cells requires dramatic changes in developmental programs. In this proposal I will examine the contributions of microRNAs (miRNAs) as modulators of changes in genetic programs during heart regeneration by focusing on the role of the key processing enzyme, Dicer and two specific miRNAs, miR-21 and miR133. For my studies, I will use the powerful, vertebrate zebrafish as a genetic model system due to its robust capacity for heart regeneration. My goal for this research is to ascertain how tissue-specific miRNAs are regulating cardiac regeneration through the use of inducible transgenic strains that modify miRNA activity. My studies will enhance potential therapies to increase survival and regeneration of adult cardiac muscle following ischemic injury.