title: Two Forkhead transcription factors regulate cardiac progenitor specification by controlling the expression of receptors of the fibroblast growth factor and Wnt signaling pathways.
abstract: 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.
authors.affiliation: Department of Biology, Indiana State University, Terre Haute, IN 47809, USA The Center for Genomic Advocacy, Indiana State University, Terre Haute, IN 47809, USA Laboratory of Developmental Systems Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA Shaad.Ahmad@indstate.edu michelsonam@nhlbi.nih.gov.
authors.forename: Shaad M
authors.initials: SM
authors.lastname: Ahmad
authors.affiliation: Laboratory of Developmental Systems Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Pritha
authors.initials: P
authors.lastname: Bhattacharyya
authors.affiliation: Office of Biostatistics Research, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Jeffries
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gisselbrecht
authors.affiliation: Laboratory of Developmental Systems Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA Shaad.Ahmad@indstate.edu michelsonam@nhlbi.nih.gov.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Michelson
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D051858:Forkhead Transcription Factors; D005346:Fibroblast Growth Factors
keywords: Cardiac mesoderm specification; Cardiac progenitor specification; Cardiogenesis; Fibroblast growth factor receptor; Forkhead domain transcription factors; Gene regulation; Heart development; Organogenesis; Signaling pathway receptors; Wnt signaling pathway receptors