Research in our laboratory focuses on the developmental biology of the heart. Cardiovascular disease is the leading cause of mortality in adults and is the principle non-infectious cause of death in children. While many treatment regimens exist, none provide a long-term cure. A number of clinical trials using bone marrow or cord blood stem cells have attempted to regenerate heart muscle after acute myocardial infarction, however, there is little or no evidence of muscle regeneration leading to largely disappointing clinical outcomes. Thus, there is a critical need to identify and activate the most primitive cardiovascular stem cells (CSCs) with the primary goal of generating replacement tissue for damaged heart muscle, valves, and vessels. Our goal is to identify the normal mechanisms by which CSCs are specified, expanded, and differentiated during embryonic development to ultimately augment the activity of either endogenous or transplanted CSCs for clinical use. The zebrafish is an excellent model system to study fate determination and stem cell biology as there are distinct genetic and transplantation advantages. As the developmental genetics of organ formation are highly conserved between fish and mammals, the pathways affecting fate decisions in zebrafish can be directly compared to that of humans. We are identifying master CSC pools within the developing teleost and dissecting their initial induction using both genetic and chemical-based screening strategies. Moreover, we are prospectively isolating these populations based on fluorescent marker gene expression and transplanting them into whole blastulae to uncover their developmental potential in vivo. Using different mutant lines, we can also reveal the effect specific mutations bear on their differentiation abilities. Through the creation of inducible heart disease models, we will transplant these embryonic populations into adult animals to investigate their regenerative capacity.