Ras Pathway Specificity Is Determined by the Integration of Multiple Signal-Activated and Tissue-Restricted Transcription Factors

• Published in: Cell 2000-09, Vol.103 (1), p.63-74
• Main Authors: Halfon, Marc S, Carmena, Ana, Gisselbrecht, Stephen, Sackerson, Charles M, Jiménez, Fernando, Baylies, Mary K, Michelson, Alan M
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins; Binding Sites - genetics; Body Patterning - genetics; Cell Lineage - genetics; DNA-Binding Proteins; Drosophila; Drosophila - embryology; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins; dTCF protein; Enhancer Elements, Genetic - genetics; Eye Proteins - genetics; Eye Proteins - metabolism; Gene Expression Regulation, Developmental - genetics; Heart - embryology; Homeodomain Proteins - genetics; Insect Proteins - genetics; Insect Proteins - metabolism; MAD protein; Mesoderm - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - embryology; Muscle, Skeletal - metabolism; Myocardium - cytology; Myocardium - metabolism; Nerve Tissue Proteins; Pointed protein; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Ras protein; ras Proteins - genetics; ras Proteins - metabolism; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Signal Transduction - genetics; Stem Cells - cytology; Stem Cells - metabolism; Tinman protein; Transcription Factors - genetics; Twist protein; Wingless protein; Wnt1 Protein
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)00105-7

Ras signaling elicits diverse outputs, yet how Ras specificity is generated remains incompletely understood. We demonstrate that Wingless (Wg) and Decapentaplegic (Dpp) confer competence for receptor tyrosine kinase–mediated induction of a subset of Drosophila muscle and cardiac progenitors by acting both upstream of and in parallel to Ras. In addition to regulating the expression of proximal Ras pathway components, Wg and Dpp coordinate the direct effects of three signal-activated (dTCF, Mad, and Pointed—functioning in the Wg, Dpp, and Ras/MAPK pathways, respectively) and two tissue-restricted (Twist and Tinman) transcription factors on a progenitor identity gene enhancer. The integration of Pointed with the combinatorial effects of dTCF, Mad, Twist, and Tinman determines inductive Ras signaling specificity in muscle and heart development.