Signal-dependent regulation of cardiac progenitor proliferation

Title: Signal-dependent regulation of cardiac progenitor proliferation Project Summary Deciphering signal-dependent coordination of cardiomyocyte proliferation during prenatal growth is essential for the diagnosis and treatment of congenital heart disorders. The complexity of this process in vertebrates has hindered progress. We have begun to exploit the extreme cellular simplicity of Ciona robusta, a close evolutionary relative of the vertebrates, to investigate potentially conserved roles for signals in coordinating cardiomyocyte lineage division dynamics. Our current hypothesis is that regional signals coordinate proliferation across distinct sub-populations of cardiac progenitors. This hypothesis is supported by evidence from our preliminary data indicating that - 1) there are two Ciona cardiomyocyte progenitor populations that exhibit distinct division patterns and proliferative frequencies, 2) sub-populations of cardiac progenitors express distinct sets of receptors and 3) disruption of candidate signaling pathways disrupts division in one of these progenitor populations. The proposed specific aims focus on determining whether regional signals directly mediate population specific proliferation patterns or indirectly influence proliferation by regulating progenitor lineage fate specification. Our efforts will initially focus on characterizing cardiomyocyte progenitor cell division dynamics. We will then identify candidate signaling pathways by using our scRNA-seq data to assess expression of signaling ligands and receptors within distinct progenitor cell types and surrounding cells. We will then begin to elucidate the role of candidate signals in cardiomyocyte lineage division and fate specification through targeted loss of function assays. These efforts will provide intensive research opportunities for a diverse group of undergraduates.