Don't Go Breaking My Heart: A Morphogenetic Role for FGF Signaling in Zebrafish Cardiac Jogging, Looping & Ballooning

Abstract

The cellular events underlying proper cardiac development require the correct interpretation of signaling cues. Congenital heart defects, which affect 1 in 100 infants in the U.S. each year, arise from a failure of these events to occur. Using zebrafish as a model, we aim to better understand the links between errors in signaling, cellular aberrations, and heart malformation. To that end, we have investigated the role of Fibroblast Growth Factor (FGF) signaling, which is known to couple morphogenesis to cell migration events in zebrafish, in asymmetric heart development. We have uncovered three windows during which FGF signaling is necessary for the later stages of heart development, independent of the pathway’s earlier role in establishing left-right asymmetry. We find that FGF signaling is critical for proper tube extension (during cardiac jogging), chamber placement (cardiac looping) and chamber expansion (cardiac ballooning). We hypothesize that FGF signaling influences cardiac jogging through interactions with the actin cytoskeleton, cardiac looping by promoting the addition of a late-differentiating pool of cardiac progenitors (second/anterior heart field) to the arterial pole of the heart tube, and cardiac ballooning by regulating cell shape changes in the curvatures of the looped heart. This study helps us to better understand how signaling pathways regulate the complex processes involved in cardiac development and how disruptions in this process result in congenital heart defects.