Alexandra Ulmer

An Analysis of the Role of Notch Signaling in Neural Crest-derived Cardiomyocytes

Mentor: Martin Tristani-Firouzi, M.D.

Department: Pediatrics

The neural crest is a stem cell population in developing vertebrates that migrates from the dorsal side of the neural tube throughout the embryo, terminally differentiating into a variety of cell types. A subpopulation of neural crest cells differentiate into cardiomyocytes (NC-Cms). In zebrafish, these cells were found to express Notch ligand jag2b. To further study these cells, we use a genetic zebrafish model to specifically ablate NC-Cms. When ablated during development, zebrafish develop adult-onset hypertrophic cardiomyopathy, likely from trabeculation defects. This phenotype is also seen in jag2b null mutants. This study aims to determine if jag2b null mutation and NC-Cm ablation result in an additive phenotype, where NC-Cm ablation and jag2b null mutation together result in a significantly more severe phenotype than either condition alone. These data will help to determine if trabeculation is regulated through Notch signaling from NC-Cms. To determine the severity of hypertrophic cardiomyopathy, heart sections were evaluated for percent tissue cover. jag2b null mutants with NC-Cm ablation were compared to control siblings (wild type fish with no abnormalities, wild type fish with NC-Cm ablation, and jag2b null mutants without NC-Cm ablation) to determine if these hearts were significantly more hypertrophic than jag2b null mutation or NC-Cm ablation alone. Ultimately, the jag2b null mutation enhanced the hypertrophic cardiomyopathy in comparison to the wild type fish, both with and without NC-Cm ablation. This suggests the strongest factor in determining adult-onset hypertrophic cardiomyopathy was the presence or absence of the jag2b gene and in turn the Notch ligand.