Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors

Ras signaling elicits diverse outputs, yet how Ras specificity is generated remains incompletely understood. We demonstrate that Wingless (Wg) and Dec apentaplegic (Dpp) confer competence for receptor tyrosine kinase-mediated induction of a subset of Drosophila muscle and cardiac progenitors by actin g both upstream of and in parallel to Pas. In addition to regulating the ex pression of proximal Ras pathway components, Wg and Dpp coordinate the dire ct effects of three signal-activated (dTCF, Mad, and Pointed-functioning in the Wg, Dpp, and Ras/MAPK pathways, respectively) and two tissue-restricte d (Twist and Tinman) transcription factors on a progenitor identity gene en hancer. The integration of Pointed with the combinatorial effects of dTCF, Mad, Twist, and Tinman determines inductive Ras signaling specificity in mu scle and heart development.