GSBS Dissertations and Theses

ORCID ID

0000-0003-0344-5550

Publication Date

2019-04-03

Document Type

Doctoral Dissertation

Academic Program

MD/PhD, Translational Science

Department

Cardiovascular Medicine

First Thesis Advisor

Chinmay Trivedi

Keywords

Cardiac Development, Development, Epigenetics, Histone Deacetylase, HDAC, Cardiovascular, Congenital Heart Disease

Abstract

Congenital heart disease is the most common congenital anomaly, affecting approximately 1% of all live births each year. Although clinical interventions are improving, many affected infants do not survive to adulthood. Congenital cardiac defects originate from disturbances during development, making the study of mammalian cardiogenesis critical to improving outcomes for infants with congenital heart disease. Development of the mammalian heart involves epigenetically-driven specification and commitment of a diverse landscape of cardiac progenitors. Recent studies determined that chromatin modifying enzymes play a previously underappreciated role in the pathogenesis of congenital heart defects. This thesis investigates the functions of Hdac1 and Hdac2, highly homologous Class I histone deacetylases, during early murine cardiac development. We establish that Hdac1 and Hdac2 cooperatively regulate cardiogenesis in distinct cardiac progenitor populations during development. Together, our findings demonstrate that Hdac1 and Hdac2 are critical mediators of the earliest stages of mammalian cardiogenesis through a variety of spatiotemporally specific, redundant, and dose-sensitive roles and indicate they may play important roles in the pathogenesis of human congenital cardiac defects.

DOI

10.13028/av6t-ay69

Rights and Permissions

Copyright is held by the author, with all rights reserved.

Available for download on Thursday, April 29, 2021

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