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Forkhead (Fkh/Fox) domain transcription factors (TFs) mediate multiple cardiogenic processes in both mammals and  Drosophila . We showed previously that the  Drosophila  Fox gene  jumeau  ( 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 other  jumu -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 and  jumu  loss-of-function mesodermal cells, we identified  nebbish  ( neb ), a kinesin-encoding gene activated by  jumu . Phenotypic analysis shows that  neb  is required for only two categories of  jumu -regulated cardiac progenitor cell division: symmetric and cell division at an earlier stage. Synergistic genetic interactions between  neb ,  jumu ,  Myb , and  polo  and the rescue of  jumu  mutations by ectopic cardiac mesoderm-specific expression of  neb  demonstrate that  neb  is an integral component of a  jumu -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.

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