Cardiogenesis, the induction and subsequent development of the heart, is a critical event during embryogenesis. Mutations of genes expressed in the early heart cause defective cardiac development, and are responsible for embryonic lethality and congenital heart disease (CHD), occurring in ~1% of live births and 10% of stillbirths in humans. T-box genes encode transcription factors that play vital roles for the development of various organs. Mutations in T-box genes (e.g., TBX1, 2, 3, 4, 5, 9 and 22) are associated with human diseases with birth defects. Tbx20 is an ancient T-box family gene with orthologues present in species from Drosophila to human. In mammals, Tbx20 is highly expressed in the developing heart, and cardiac expression is maintained from embryonic stages to adulthood, indicating that Tbx20 plays important roles for heart formation and function. My previous studies have demonstrated that disruption of Tbx20 leads to embryonic lethality due to defects in early heart development (E9.5-E10.5 in mouse), while the role of Tbx20 at later embryonic stages (E10.5-neonate in mouse) is still largely unknown. Our goals are to characterize the roles of Tbx20 in the development of epicardial cells, and in the development of heart at middle-late gestational stage (E10.5-E18.5 in mouse). In addition, we are also interested in deciphering the regulatory network of Tbx20 in order to fully understand how this important transcription factor effects heart development and function. Towards these goals, our Specific Aims are: 1). To investigate the role of Tbx20 in epicardial development during mouse embryogenesis. 2). To investigate the role of Tbx20 in heart development and function at middle and late gestation. 3). To characterize the transcriptional network of Tbx20. Results from these studies will provide a comprehensive overview of Tbx20 with respect to heart development and function. Moreover, it may also provide new insights into the etiology of human CHD resulting from perturbations in TBX20 and its target genes. Career Plan:Career goal of the PI is to become a highly successful investigator in the basic science of cardiovascular development and cardiac stem cell biology through support of this K02 award. Institute Environment: Mount Sinai School of Medicine is a prestigious biomedical research institute and research proposed in this study is fully supported by the school at the institutional level.
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