Synergistic and independent roles for Nodal and FGF in zebrafish cardiac progenitor cell migration and asymmetric heart morphogenesis

Abstract

Asymmetric development of the vertebrate heart is driven by a complex sequence of morphogenetic cell movements, coordinated through precise interpretation of signaling cues by the heart primordia. Here, we show that Nodal signaling functions synergistically with FGF to stimulate the migration of cardiac progenitor cells (CPCs) during cardiac jogging - the first morphological asymmetry observed in zebrafish heart development. While Nodal directs the asymmetric migration of CPCs, we find FGF signaling to be dispensable for this asymmetry, suggesting that FGF plays a permissive rather than instructive role. We further demonstrate that Nodal signaling induces asymmetries in actin cytoskeletal dynamics that correlate with the directional migration of CPCs, whereas FGF does not influence this actin asymmetry. In addition to influencing jogging, FGF and Nodal synergize to ensure proper heart looping. We also provide evidence that FGF contributes to heart looping by promoting the differentiation of the second heart field. Together, these findings offer insight into how the spatiotemporal dynamics of signaling pathways regulate the cellular behaviors driving organ morphogenesis.