Scraps, an anilin, and Nebbish, a kinesin, are integral components of a Fox transcription factor-regulated subnetwork that mediates specific cardiac progenitor cell divisions
Authors: Md Rezaul Hasan 1,2,3; Rajnandani Katariya 1,2; Andrew Kump 1,2,3; Manoj Panta 1,2; Kristopher Schwab 1,2,3; Mark Inlow 2,4; Shaad Ahmad 1,2,3
Affiliations: 1) Department of Biology, Indiana State University, Terre Haute, IN; 2) The Center for Genomic Advocacy, Indiana State University, Terre Haute, IN; 3) Rich and Robin Porter Cancer Research Center, Indiana State University, Terre Haute, IN; 4) Department of Mathematics and Computer Science, Indiana State University, Terre Haute, IN
Keywords: t. mesodermal derivatives; p. transcriptional regulation
Forkhead/Fox transcription factors (TFs) mediate multiple cardiogenic processes in both mammals and Drosophila. We showed previously that the Drosophila Fox genes jumeau (jumu) and Checkpoint suppressor 1-like (CHES-1-like) control three categories of cardiac progenitor cell division—asymmetric, symmetric, and cell division at an earlier stage—by regulating Polo kinase activity, and mediate the latter two categories in concert with the TF Myb. Those observations raised two questions: whether other Fox TF-controlled genes mediating cardiac progenitor cell divisions were also regulated by both CHES-1-like and jumu in a polo-like manner and whether such Fox-regulated genes mediated all three categories of cardiac progenitor cell division or a subset thereof. By comparing transcriptional expression profiles of wild-type, jumu loss-of-function, and CHES-1-like loss-of-function mesodermal cells, we identified multiple genes transcriptionally activated by jumu, but not regulated by CHES-1-like. Phenotypic analysis of mutations showed that two of these exclusively jumu-regulated targets, the kinesin-encoding gene nebbish (neb) and the anilin-encoding gene scraps (scra) are required for only two of the three categories of jumu-regulated cardiac progenitor cell division: symmetric and cell division at an earlier stage. Synergistic genetic interactions between neb, scra, jumu, and polo; between neb and Myb; the absence of such synergistic interactions between either scra and CHES-1-like or neb and CHES-1-like; and the rescue of solely symmetric and earlier cardiac progenitor cell division defects in jumu mutants by ectopic cardiac mesoderm-specific expression of neb demonstrate that scra and neb comprise an exclusively jumu-regulated subnetwork mediating a specific subset of cardiac progenitor cell divisions. Preliminary data from our phenotypic analysis of other exclusively jumu-regulated genes suggests that the kinesin-encoding gene pavarotti, the citron kinase-encoding gene sticky, and the Rho GTPase-encoding gene tumbleweed may be other components of this subnetwork. Using additional genetic interaction and rescue assays, we are attempting to position neb and scra topologically relative to each other and these other potential subnetwork components. Collectively, our results illustrate how an individual regulator can utilize different combinations of downstream effectors to control distinct developmental processes.