Nodal Directs Asymmetric Cardiac Morphogenesis Through Regulation of Actin Cytoskeleton

Abstract

Abstract

Asymmetries in the zebrafish heart are established through a series of dynamic cell

migrations. The first migration event, known as cardiac jogging, consists of the

conversion of the cardiac cone into the linear heart tube. Recent work from our lab has shown that the laterality of cardiac jog is directed by Nodal signals that increase cell migration rates of the left atrial cells. Although we now know that Nodal increases cell migration rates, the downstream cellular responses to Nodal signaling in cardiac cells remains to be explored. In this study, we utilize a microarray approach to identify novel transcriptional targets of Nodal signaling within the heart. The data suggest that Nodal influences several pathways and genes, including those that regulate the actin cytoskeleton. Inhibition of cdc42 regulated actin polymerization produces a migration defect that appears to be specific to the cardiac cone. To gain further insights into the in vivo regulation of cytoskeletal dynamics, we utilized lifeact:RFP and uncovered dynamic Nodal-dependent changes in actin polymerization just prior to cardiac jogging. Further, we provide evidence that fgd1, a cdc42 specific GEF, is transcriptionally regulated by Nodal signaling and functions in the asymmetric cell migration that leads to cardiac jogging. Together, our results reveal a novel role for Nodal signaling in regulating actin polymerization within the cardiac cone to control the migration behavior necessary to achieve proper laterality.