The Drosophila Forkhead/Fox transcription factor Jumeau mediates specific cardiac progenitor cell divisions by regulating expression of the kinesin Nebbish

Abstract

AbstractForkhead (Fkh/Fox) domain transcription factors (TFs) mediate multiple cardiogenic processes in both mammals andDrosophila. We showed previously that theDrosophilaFox genejumeau(jumu) controls three categories of cardiac progenitor cell division—asymmetric, symmetric, and cell division at an earlier stage—by regulating Polo kinase activity, and mediates the latter two categories in concert with the TF Myb. Those observations raised the question of whether otherjumu-regulated genes also mediate all three categories of cardiac progenitor cell division or a subset thereof. By comparing microarray-based expression profiles of wild-type andjumuloss-of-function mesodermal cells, we identifiednebbish(neb), a kinesin-encoding gene activated byjumu. Phenotypic analysis shows thatnebis required for only two categories ofjumu-regulated cardiac progenitor cell division: symmetric and cell division at an earlier stage. Synergistic genetic interactions betweenneb,jumu,Myb, andpoloand the rescue ofjumumutations by ectopic cardiac mesoderm-specific expression ofnebdemonstrate thatnebis an integral component of ajumu-regulated subnetwork mediating cardiac progenitor cell divisions. Our results emphasize the central role of Fox TFs in cardiogenesis and illustrate how a single TF can utilize different combinations of other regulators and downstream effectors to control distinct developmental processes.