Presenter(s): Diana Nguyen − Biology, Human Physiology
Faculty Mentor(s): Gabriel Yette, Kryn Stankunas
Poster 48
Research Area: Genetics, Heart Development, Biology
Funding: O’Day Fellowship in Biological Sciences and the Office of the Vice President for Research and Innovation
Nearly 1% of individuals are born with a congenital heart defect (CHD), making CHDs the most common birth defect. Understanding the genetic and epigenetic underpinnings of heart development has the potential to aid in developing tools to diagnose and treat CHD. It is increasingly evident that chromatin structure and histone modifications play essentiaL roles in heart development and homeostasis. A histone modification of interest is the tri-methylation of lysine 27 of histone H3 (H3K27me3), which is associated with gene repression. This modification is catalyzed by EZH2, the methyltransferase component of Polycomb Repressive Complex 2 (PRC2), and can be removed by Kdm6 family of demethylases. Recent work in the Stankunas lab shows that disruption of Kdm6ba and Kdm6bb in zebrafish result in smaller, poorly trabeculated ventricles of the heart. Interestingly, hearts of mice with Cre/lox dependent knockdown of Ezh2 exhibit hyper-trabeculation, ventricular septation, thinning of the ventricular wall, and aberrant skeletal muscle gene activation. These studies highlight the proper maintenance of H3K27me3 necessary for proper development. Yet, the effects of EZH2 on heart development in zebrafish has not been well explored. Zebrafish are ideal for investigating the early stages of heart development since they are transparent, and develop outside the mother, allowing for easy observation of the heart during this crucial period; elements that evades the Cre/lox system in mice. We generated an ezh2-null allele allowing us to conduct heart development studies. We hypothesize that PRC2/EZH2 is necessary to establish and maintain cardiomyocyte cellular identity by repressing developmental pathways of similar tissue types. For this project, we aim to: 1) Establish when and where EZH2 is expressed in the heart during development, and 2) Determine morphological and functional changes in developing hearts of ezh2 null zebrafish.