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The embryonic heart elongates by addition of epithelial progenitor cells from the second heart field to the growing arterial and venous cardiac poles. Failure of this process results in congenital heart defects. The T-box transcription factors Tbx1 and Tbx5, major genes implicated in 22q11.2 and Holt-Oram Syndrome respectively, demarcate anterior and posterior second heart field subpopulations giving rise to arterial and venous pole myocardium. Recent work has shown that these subdomains originate in a common progenitor population and that differential epithelial cell properties, including adhesion, shape and tension, accompany the segregation of arterial and venous pole progenitor cells. However, how patterning events are coupled to the epithelial properties of the progenitor cell field is unknown. Our project aims to characterise the genetic and cellular mechanisms driving progenitor cell patterning in the epithelial second heart field. We will use mouse genetics, imaging and transcriptomics to define regulatory events upstream and downstream of Tbx1 and Tbx5 and their impact on the epithelial properties of second heart field cells.
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