Date of Award

2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Abstract

Congenital heart defects (CHD) are the most common developmental abnormalities seen at birth. Therefore, it is critical to understand the molecular mechanisms that ensure cardiogenesis proceeds correctly. These mechanisms include those facilitated by the essential evolutionarily conserved Trithorax Group (TrxG) and Polycomb Group (PcG) protein complexes that govern proper gene expression during development and cardiogenesis. The Drosophila melanogaster dorsal vessel, a linear tube composed of both contractile cardial cells (CCs) from Seven-up (Svp) and Tinman (Tin) lineages and nephrocytic pericardial cells (PCs), has served as an excellent model system to uncover the roles of genes regulating proper cardiogenesis in mammals. Scientific investigations in Drosophila melanogaster have allowed us to uncover many of the key molecular mechanisms governing heart development. This, among many other reasons that will be discussed later, make Drosophila melanogaster a remarkable system for understanding how cardiogenesis is regulated. In the first section of this work (Chapter 2), the role of the TrxG COMPASS-like Trr (Trithorax-related) complex in regulating proper cardiogenesis in the stage 16 Drosophila melanogaster dorsal vessel is assessed. The COMPASS-like Trr complex members Ptip and trr were found to facilitate proper symmetric Tin-CC and Svp cardiac progenitor cell division. Additional experiments provide evidence that Ptip and trr also genetically interact to facilitate proper symmetric Tin-CC and likely earlier Svp cardiac progenitor cell division as critical components of the Trr complex. In the second section of this work (Chapter 3), the division of labor among the TrxG COMPASS-like complex histone methyltransferases in regulating cardiac development was assessed by examining the stage 16 dorsal vessel. trithorax ( trx ) is shown to be uniquely critical among the COMPASS-like complex histone methyltransferases for proper regulation of anterior-posterior patterning and Hox gene expression in the Drosophila melanogaster dorsal vessel. The disruption in Hox gene expression patterns lead to a combination of phenotypes that alter dorsal vessel patterning and morphology. Finally, the last part of this work (Chapter 4) focuses on the roles of the PcG member Polycomb ( Pc ), a gene known to antagonize trx function, in regulating cardiac development. Pc is shown to be essential for repressing posterior cardiac Hox gene expression and repressing a heart proper-like fate within the aorta of the stage 16 dorsal vessel. The findings presented in this work add critical knowledge to the scientific understanding of how the TrxG and PcG regulate cardiac cell division and patterning. Additionally, these findings raise many important questions about the precise molecular mechanisms by which Hox gene expression is regulated during cardiogenesis.

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