Coronary vessel development and regulation of cardiac morphogenesis

基本原理：心脏发育是一个复杂的过程，需要紧密协调的多组织计划才能实现成功的成熟和功能。需要不同的组件来构建成人心脏。心脏血管，称为冠状动脉，为心肌提供血液和营养，由心肌细胞组成。心肌确保血液和营养物质持续有效地供应到身体的其他部位。有趣的是，冠状动脉发展的开始与特别是心肌和一般心脏经历增殖和生长显著增加的阶段相一致。冠状动脉如何调节心脏发育？冠状动脉血管在发育过程中发挥的作用与成人心脏不同吗？我们的研究计划旨在确定冠状动脉网络如何积极控制心脏发育，功能和成熟的各个方面。为此，我们将利用斑马鱼模型，其中冠状动脉网络在幼年阶段（子宫外）发育，并允许对其发育进行仔细和详细的研究。目的和假设：作为本项目的一部分，我们将建立一个全面的路线图冠状动脉网络形成整个发展。此外，我们将研究冠状血管如何与其他心肌细胞相互作用，特别关注心肌细胞。我们假设，除了作为运输系统的作用外，冠状动脉还为发育中的心肌细胞提供指导线索，心肌细胞反过来又沿着这些血管的轨迹填充心室表面并构建成熟的心脏壁。相关性：长期以来，血管被认为是作为运输系统发挥其唯一功能。在这个项目中，我们将首次描述斑马鱼冠状血管的发育和模式。这些数据将使我们能够建立冠状动脉血管发育，规格和图案的参考地图，并将构成该领域未来研究的基础。重要的是，血管旁分泌调节的新概念在心脏发育过程中仍然很大程度上未被探索。因此，确定调节心脏发育和心肌细胞生物学的冠状动脉血管线索将对心血管生物学以外的领域具有重要意义，并对加拿大的血管研究具有战略意义。

Rationale: Cardiac development is a complex process that requires a tightly coordinated multi-tissue program to achieve successful maturation and function. Different components are required to build the adult heart. Cardiac vessels, termed coronaries, supply blood and nutrients to the cardiac muscle, composed of cardiomyocytes. The cardiac muscle ensures a constant and efficient supply of blood and nutrients to the rest of the body. Interestingly, the onset of coronary development coincides with stages where the cardiac muscle in particular, and the heart in general, experience significant increases in proliferation and growth. How do coronary vessels regulate cardiac development? Do coronary vessels play a different role during development than in adult hearts? Our research program aims to determine how the coronary network actively controls various aspects of heart development, function, and maturation. To this end, we will utilize the zebrafish model where the coronary network develops at juvenile stages (ex utero) and allows careful and detailed studies of its development. Objective and hypothesis: As part of this project, we will build a comprehensive road map of coronary network formation throughout development. Moreover, we will investigate how coronary vessels interact with other cardiac cells, paying special attention to cardiomyocytes. We hypothesize that, beyond their role as a transport system, coronaries provide guidance cues to developing cardiomyocytes, which in turn follow the track of these vessels to populate the ventricular surface and build the mature cardiac wall. Relevance: Blood vessels have been long considered to serve as a transport system as their only function. In this project, we will characterize for the first time how zebrafish coronary vessels develop and pattern. These data will allow us to build a reference map for coronary vessel development, specification, and patterning and will constitute the basis for future research in the field. Importantly, the emerging concept of vessel paracrine regulation remains largely unexplored during cardiac development. Therefore, identifying coronary vascular cues regulating heart development and cardiomyocyte biology will be of great significance to fields beyond cardiovascular biology and of strategic interest to vascular research in Canada.