title: Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors.
abstract: 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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Halfon
authors.forename: A
authors.initials: A
authors.lastname: Carmena
authors.forename: S
authors.initials: S
authors.lastname: Gisselbrecht
authors.forename: C M
authors.initials: CM
authors.lastname: Sackerson
authors.forename: F
authors.initials: F
authors.lastname: Jiménez
authors.forename: M K
authors.initials: MK
authors.lastname: Baylies
authors.forename: A M
authors.initials: AM
authors.lastname: Michelson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006321:Heart / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D051155:Wnt1 Protein; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C076188:AOP protein, Drosophila; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C052837:eve protein, Drosophila; C083884:pnt protein, Drosophila; C074622:wg protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins