Genetic and Molecular Investigation of Tbx20 in Cardiac Development Project Summary: 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 (TFs) 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. Given the conserved expression of Tbx20 in cardiac tissues across species, we hypothesize that Tbx20 is a key transcription factor (TF) that extensively contributes to cardiac development and function from early embryonic stage to adulthood in mammals. My previous studies have revealed that disruption of Tbx20 leads to embryonic lethality due to proliferative defects of early chamber myocardium (E9.5-E10.5 in mouse), while the roles of Tbx20 for non- chamber myocardial development are still largely unknown. Our long-term objectives are to study the biology of Tbx20 in order to obtain a comprehensive understanding of how this important TF regulates heart development, and how dysfunction of Tbx20 correlates with human CHD. In this study, we will specifically examine the role of Tbx20 in the development of three key cardiac components- the outflow tract (OFT), atrioventricular canal (AVC), and epicardium. In further, we will decipher the regulatory network of Tbx20 in order to fully understand how this important TF mechanistically effects heart formation and function.
Our study uses mouse as a model system to examine the role of T-box transcription factor Tbx20 in the development of epicardium, outflow tract and atrioventricular canal of the heart. We will also examine regulatory network of Tbx20 in order to fully understand how this gene effects heart formation and function.
