期刊
DEVELOPMENT
卷 143, 期 2, 页码 306-317出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.122952
关键词
Forkhead domain transcription factors; Signaling pathway receptors; Fibroblast growth factor receptor; Wnt signaling pathway receptors; Gene regulation; Cardiac progenitor specification; Cardiac mesoderm specification; Heart development; Cardiogenesis; Organogenesis
资金
- National Heart, Lung, and Blood Institute (NHLBI) Division of Intramural Research
Cardiogenesis involves the coordinated regulation of multiple biological processes by a finite set of transcription factors (TFs). Here, we show that the Forkhead TFs Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu), which govern cardiac progenitor cell divisions by regulating Polo kinase activity, play an additional, mutually redundant role in specifying the cardiac mesoderm (CM) as eliminating the functions of both Forkhead genes in the same Drosophila embryo results in defective hearts with missing hemisegments. This process is mediated by the Forkhead TFs regulating the fibroblast growth factor receptor Heartless (Htl) and the Wnt receptor Frizzled (Fz): CHES-1-like and jumu exhibit synergistic genetic interactions with htl and fz in CM specification, thereby implying that they function through the same genetic pathways, and transcriptionally activate the expression of both receptor-encoding genes. Furthermore, ectopic overexpression of either htl or fz in the mesoderm partially rescues the defective CM specification phenotype in embryos lacking both Forkhead genes. Together, these data emphasize the functional redundancy that leads to robustness in the cardiac progenitor specification process, and illustrate the pleiotropic functions of Forkhead TFs in different aspects of cardiogenesis.
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