Coronary vessel development and regulation of cardiac morphogenesis

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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.