title: Initial deployment of the cardiogenic gene regulatory network in the basal chordate, Ciona intestinalis.
abstract: The complex, partially redundant gene regulatory architecture underlying vertebrate heart formation has been difficult to characterize. Here, we dissect the primary cardiac gene regulatory network in the invertebrate chordate, Ciona intestinalis. The Ciona heart progenitor lineage is first specified by Fibroblast Growth Factor/Map Kinase (FGF/MapK) activation of the transcription factor Ets1/2 (Ets). Through microarray analysis of sorted heart progenitor cells, we identified the complete set of primary genes upregulated by FGF/Ets shortly after heart progenitor emergence. Combinatorial sequence analysis of these co-regulated genes generated a hypothetical regulatory code consisting of Ets binding sites associated with a specific co-motif, ATTA. Through extensive reporter analysis, we confirmed the functional importance of the ATTA co-motif in primary heart progenitor gene regulation. We then used the Ets/ATTA combination motif to successfully predict a number of additional heart progenitor gene regulatory elements, including an intronic element driving expression of the core conserved cardiac transcription factor, GATAa. This work significantly advances our understanding of the Ciona heart gene network. Furthermore, this work has begun to elucidate the precise regulatory architecture underlying the conserved, primary role of FGF/Ets in chordate heart lineage specification.
authors.affiliation: Department of Molecular and Cellular Biology, Molecular Cardiovascular Research Program, University of Arizona, Arizona 85724, USA.
authors.forename: Arielle
authors.initials: A
authors.lastname: Woznica
authors.forename: Maximilian
authors.initials: M
authors.lastname: Haeussler
authors.forename: Ella
authors.initials: E
authors.lastname: Starobinska
authors.forename: Jessica
authors.initials: J
authors.lastname: Jemmett
authors.forename: Younan
authors.initials: Y
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Mount
authors.forename: Brad
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000818:Animals; D001483:Base Sequence; D019070:Cell Lineage / Q000235:genetics; D002938:Ciona intestinalis / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006321:Heart / Q000196:embryology; D017403:In Situ Hybridization; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D059372:Nucleotide Motifs / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D005346:Fibroblast Growth Factors