Date of Award

1-30-2001

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Mark D.|Carlson, Edward Olson

Abstract

The definitive origin(s) of endothelial cell precursors involved in establishing the endothelial lining of intramural coronary vasculature within the subepicardial space of the embryonic chick heart have not been fully characterized. This vasculogenic process is suggested to derive from reciprocal tissue interactions between the myocardium, dorsal mesocardium, and continuous epicardium. These developmental processes occur in chick embryos, staged 16–25 (2 to 4.5–5 days). In the current study, presumptive endothelial precursor cells have been located amongst the surface epithelial cells of the dorsal mesocardium and villi of the proepicardial organ, both of which contribute to the epicardial epithelium. Endothelial precursor cells have also been located within the continuous connective tissue space of the dorsal mesocardium and the subepicardial space. Coronary vessel development corresponds spatially and temporally with the migration and establishment of the epicardial epithelium as it forms the underlying subepicardial space. Flk-1 (fetal liver kinase-1), a tyrosine kinase receptor for VEGF (vascular endothelial growth factor), has been shown to regulate the mechanism of vasculogenesis during embryogenesis. Furthermore, flk-1 has been shown to be restricted to endothelial cells and their precursors after day two in quail embryos. Thus, flk-l mRNA is the earliest currently available known indicator of endothelial cell precursors. In the current study, in situ hybridization was used to study the location of flk-1 mRNA in endothelial cells and their precursors in the chick by labeling heart tissue sections with sense and antisense probes. This probe detected flk-1 receptor mRNA in cells destined to become endothelial cells prior to vessel formation. Flk-l receptor mRNA was detected in endothelial precursor cells located within the epicardial epithelium, the epicardial organ, and the connective tissue space of the dorsal mesocardiurn and subepicardial space. The results of the present study supported the hypothesis that endothelial cell precursors contributing to intramural coronary vasculogenesis within the subepicardial space originate from the epicardial epithelium and its presumptive origins as well as from the mesenchyme migrating through the dorsal mesocardium.

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