Assessing the role of hemodynamics in embryonic development

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The cardiovascular system is the first functional organ in the embryo, and proper functioning of the early cardiovascular system is essential for embryonic health and survival. The blood vessels of the embryo are initially established by a process called vasculogenesis which occurs in the absence of blood flow.  These early vessels are then remodeled through a secondary process that is known to be dependent on the presence of blood flow. In recent years, there has been a debate regarding which aspects of early vascular formation are genetically predetermined, and which are governed by external stimuli, such as mechanical and biochemical signaling.   Though the initial vascular network is patterned without physiological feedback, once flow has begun, a separate set of physical and metabolic signals arise.  Blood pressure, blood flow, and related physical forces such as circumferential wall stress and wall shear stress as well as metabolic information such as nutrient and oxygen requirements all can provide feedback to genetically encoded signaling mechanisms. The point at which the switch from genetic mechanisms to physiological feedback mechanisms occurs remains largely unexplored.  I propose using combination of high-speed microscopy, flow visualization techniques such as DPIV and computational modelling to further investigate the relative role of genetic predetermination and hemodynamics in early cardiovascular development.  By applying these methods to the embryonic microvasculature, I will be able to investigate questions about early vascular developments such as when the early vasculature begins to receive patterning cues from blood flow, rather than from genetics.