Identification of multipotent cardiac progenitors has provided fresh insight into the mechanisms of myocardial lineage specification, yet has done little to clarify the origin of the endocardium. Despite its essential role in heart development, the lineage classification of endocardium has remained undefined due to a lack of specific markers of this early vascular subpopulation. To distinguish endocardium from other vasculature, we generated an NFATc1-nuc-LacZ BAC transgenic mouse line that faithfully recapitulated endogenous NFATc1 expression in the heart and other cell populations during development. Utilizing this novel specific marker, the endocardium can be distinguished from other endothelial subpopulations, and tracked as it emerges from the cardiac mesoderm and participates in early cardiac morphogenesis.
To further characterize endocardiogenesis, embryonic stem cells (ESCs) derived from NFATc1-nuc-LacZ blastocysts were utilized to demonstrate that endocardial differentiation occurs in a pattern consistent with its mesodermal origin and its close association with myocardium. Endocardium is specified as a cardiac cell lineage, independent from other vascular populations, responding to BMP and Wnt signals that enhance cardiomyocyte differentiation. Furthermore, a population of Flk1+ cardiovascular progenitors, distinct from hemangioblast precursors, represents a mesodermal precursor of the endocardial endothelium, as well as other cardiovascular lineages. Taken together, this work emphasizes the endocardium as a unique cardiac lineage and provides further evidence that endocardium and myocardium are derived from a common precursor. Furthermore, we have established a method to identify the endocardium at the onset of differentiation and throughout subsequent stages of development, providing the framework for future work to delineate mechanisms important in the ontogeny of this unique population.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12052008-144450 |
| Date | 30 December 2008 |
| Creators | Misfeldt, Andrew Michael |
| Contributors | Antonis Hatzopoulos, Guoqiang Gu, Tsutomu Kume, H. Scott Baldwin, Christopher V.E. Wright |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12052008-144450/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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