Fig. 8.
Distinct developmental subnetworks regulate cardiac progenitor cell division and specification. (A) Schematic of Jumu, CHES-1-like and Myb regulation of cardiac progenitor cell divisions by Polo kinase. The forkhead TFs Jumu and CHES-1-like regulate Polo kinase activity to mediate three distinct classes of cardiac progenitor cell divisions: asymmetric cell divisions, symmetric cell divisions, and an earlier round of cell division that determines the number of Svp progenitors (Ahmad et al., 2012). Mutations in Myb result in defects in only the latter two categories of cell divisions, which also exhibit synergistic genetic interactions among Myb, jumu, CHES-1-like and polo. As Myb transcriptionally regulates polo (Wen et al., 2008), Myb and the forkhead TFs act in concert to control Polo activity and thus govern both the symmetric and earlier class of cell divisions. (B) Schematic of the involvement of the Notch signaling pathway in the lineage decision between PCs and CCs for PC enhancers like that of Him. Modes of regulation activating and repressing target genes are shown as green and red arrows, respectively. In CCs, the enhancers of PC genes are repressed by the Su(H)-co-repressor complex. The Delta ligand expressed by CCs activates Notch receptor in neighboring PCs, with the resulting cleaved Nicd fragment associating with Su(H) and displacing the co-repressor. The consequent elimination of repressor complex binding in PCs is sufficient to initiate transcription due to the presence of other local TF activators, and is enhanced further by the Nicd-Su(H) complex.