title: Transcriptional integration of competence modulated by mutual repression generates cell-type specificity within the cardiogenic mesoderm.
abstract: The way in which spatially patterned cellular identities are generated is a central question of organogenesis. In the case of Drosophila heart formation, the cardiac progenitors are specified in precise mesodermal positions, giving rise to multiple cell types in a highly ordered arrangement. Here, we study the mechanisms by which positional information conveyed by signaling pathways and a combinatorial code of activating and repressing transcription factors work together to confine the expression of the homeobox gene even-skipped (eve) to a small region of the dorsal mesoderm. By manipulating both expression patterns and binding sites for transcription factors, we show that a complex combination of regulatory activities converge on a single enhancer of eve to generate precisely targeted gene expression within the cardiac mesoderm. In particular, ladybird early (lbe), a homeobox gene expressed adjacent to eve, restricts the positive actions of factors downstream of wingless, decapentaplegic, and ras to generate the eve pattern. Mutation of a Lbe binding site causes dramatic expansion of expression and abolishes the responsiveness to repression by lbe. Conversely, eliminating eve in the mesoderm expands lbe expression into the normal eve-expressing territory, suggesting that mutual repression between eve and lbe is essential for delineating the spatial patterns of gene expression that specify cell types within the cardiac mesoderm.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
authors.forename: Miki
authors.initials: M
authors.lastname: Fujioka
authors.forename: Mingtsan
authors.initials: M
authors.lastname: Su
authors.forename: Margaret
authors.initials: M
authors.lastname: Liu
authors.forename: James B
authors.initials: JB
authors.lastname: Jaynes
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D004247:DNA; D004330:Drosophila / Q000196:embryology; D024202:Electrophoretic Mobility Shift Assay; D005801:Genes, Homeobox; D006321:Heart / Q000196:embryology*; D008648:Mesoderm; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D014158:Transcription, Genetic
chemical_list: D004247:DNA