As the heart develops, forces that arise from contractility and blood flow trigger changes in various cardiac tissues, including the myocardium, endocardium and endothelium. However, understanding the mechanistic basis of these changes, and how they help sculpt the final shape of the heart, has been a challenge. Here, Deborah Yelon and colleagues investigate how forces drive assembly of the zebrafish cardiac outflow tract (OFT) – the structure that connects the developing heart to the vasculature. They first show that expansion of the OFT involves changes in the number, shape and size of both myocardial and endocardial cells. They further demonstrate that both the proliferation and addition of endocardial cells contribute to OFT expansion. Following on from this, the authors examine OFT development in troponin T type 2a mutant embryos, which lack cardiac contractility and, hence, blood flow, and report that cardiac function regulates both endocardial proliferation and endothelial addition during OFT expansion. Finally, the researchers demonstrate that the flow-responsive TGFβ receptor Acvrl1 is required for the addition of endocardial cells to the OFT, but not for their proliferation, highlighting that these two processes are regulated by distinct mechanisms. Overall, these findings provide new insights into the mechanisms that drive OFT morphogenesis and that could be implicated in cardiac birth defects.
