Transcriptional integration of competence modulated by mutual repression generates cell-type specificity within the cardiogenic mesoderm

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 posit ions, 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 The expression into the normal eve-expressing territory, suggesting that mutual repression between eve and The is essential for delineating the spatial patterns of gene expression that specify cell types within the cardiac mesoderm. (C) 2002 Elsevier Science (USA).