Proper formation of the heart during embryonic development is important for later heart function in the adult. Defects in heart formation can lead to congenital heart defects (CHD), which are present at birth. Understanding the molecular signaling pathways that regulate embryonic heart development is important for understanding how CHD form and for designing potential therapies for CHD. We study heart development using zebrafish embryos because zebrafish display similar organ structures to humans. The zebrafish heart has two chambers, the atrium and the ventricle. There are two valves, one between the atrium and the ventricle, and one at the exit, or outflow tract, of the ventricle. These valves are critically important for proper directional blood flow through the heart. Additionally, as the heart grows, cells are added to the outflow tract to increase heart size. We study heart development using a novel zebrafish valve mutant, which displays cardiovascular defects including regurgitating blood flow, which suggests a valve defect is present in these animals. To begin determining the nature of the heart defects present in the valve mutants, we analyzed heart function by quantifying the heart rate. We found a significant reduction in the mutant heart rate. Furthermore, we analyzed the expression of genes elnb1 in the outflow tract and notch1b in the heart valves. We found that the mutant displayed reduced elnb expression in the outflow tract compared to full expression in the sibling. Furthermore, mutants displayed reduced notch1b expression in the valves that also expanded outside the expected expression domain. From these results, we conclude that there is a difference in heart function, valve development, and outflow tract development in these mutants, leading to advanced cardiovascular defects. Future studies will include using linkage mapping to determine the site of the mutation that leads to the observed defects in valve mutants.
Authors: Lily Hofman, Morgan Beck, Natalie Sobel
Faculty Advisor: Jennifer Schumacher, Biological Sciences
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