Date of Award

6-2017

Document Type

Thesis

Degree Name

Master of Science in Biology

Department

Biology

First Reader/Committee Chair

Bournias-Vadiabasis, Nicole

Abstract

Coronary heart disease is a prevalent issue in developed countries throughout the world. It can have crippling effects on the quality of life and even lead to mortality, in the case of myocardial infarction. Part of the problem is the lack of a robust regenerative response in mammals after injury. Zebrafish have an amazing ability to regenerate after injury, and studies have demonstrated that the regenerative response recapitulates embryonic development. Our lab previously reported the first analysis of coronary vessel development in zebrafish and demonstrated that coronary endothelial cells undergo angiogenesis to form a vascular network. The roles of perivascular cells in this process have not been examined in zebrafish. Using a transgenic reporter line marking pdgfrb expression, I found that pdgfrb is first observed in epicardium at the AV canal. At later stages of coronary vessel development, pdgfrb positive cells become localized to the perivascular region of mature vessels. I also observe that early in development, Tcf21 and pdgfrb co-express, which suggests a close relationship between the epicardium and pdgfrb+ cells. Previous findings from our lab revealed that cxcl12b+ cells localize to large coronary vessels during development. My findings reveal that pdgfrb+ marks perivascular cells of both capillaries and large coronary vessels. Lineage tracing analysis revealed that a subset of pdgfrb+ perivascular cells derive from tcf21 labeled epicardial cells. To see if disruption of Pdgfrb signaling impacts coronary development, I examined pdgfrb mutant hearts. In the Pdgfrb mutant, a mature coronary vessel network fails to form, and instead we observe isolated endothelial cell islands. Lastly, I characterized a transgenic line that expresses a dominant negative form of Pdgfrb (dnpdgfrb) and can be potentially used for later developmental and/or regenerative studies. My findings indicate strong dnpdgfrb induction can be achieved at adult stages. My studies will greatly enhance our current understanding of coronary vessel development, and can be used as the basis for studying perivascular cells and their interactions with endothelial cells after cardiac injury in regeneration.

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