Coronary vessel development and regulation of cardiac morphogenesis

冠状血管发育和心脏形态发生的调节

• 批准号: RGPIN-2021-03011
• 负责人: MarinJuez, Ruben
• 金额: $ 2.77万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742330
• 关键词: Coronary; vessel; development; regulation; cardiac

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.

原理：心脏发育是一个复杂的过程，需要一个紧密协调的多组织程序来实现成功的成熟和功能。构建成人心脏需要不同的成分。心脏血管，称为冠脉，为心肌供应血液和营养物质，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，冠状动脉发育的开始恰逢心肌尤其是心脏的增殖和生长显著增加的阶段。冠状动脉是如何调节心脏发育的？冠状动脉在发育过程中的作用是否与成人心脏不同？我们的研究计划旨在确定冠状动脉网络如何主动控制心脏发育、功能和成熟的各个方面。为此，我们将利用斑马鱼模型，在该模型中，冠状动脉网络在幼年期(体外)发育，并允许仔细和详细地研究其发育。目标和假设：作为该项目的一部分，我们将构建一个在整个发育过程中冠状动脉网络形成的全面路线图。此外，我们将研究冠状动脉如何与其他心肌细胞相互作用，特别是心肌细胞。我们假设，除了作为运输系统的作用外，冠脉还为发育中的心肌细胞提供指导信号，心肌细胞继而跟随这些血管的轨迹填充到心室表面并构建成熟的心壁。相关性：长期以来，血管一直被认为是运输系统，是它们唯一的功能。在这个项目中，我们将首次描述斑马鱼冠状动脉的发育和模式。这些数据将使我们能够建立冠状动脉发展、规格和模式的参考图，并将构成该领域未来研究的基础。重要的是，在心脏发育过程中，血管旁分泌调节的新兴概念在很大程度上仍未被探索。因此，识别调控心脏发育和心肌细胞生物学的冠脉血管信号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。