title: EGFR signalling inhibits Capicua-dependent repression during specification of Drosophila wing veins.
abstract: Localised activation of the Ras/Raf pathway by Epidermal Growth Factor Receptor (EGFR) signalling specifies the formation of veins in the Drosophila wing. However, little is known about how the EGFR signal regulates transcriptional responses during the vein/intervein cell fate decision. We provide evidence that EGFR signalling induces expression of vein-specific genes by inhibiting the Capicua (Cic) HMG-box repressor, a known regulator of embryonic body patterning. Lack of Cic function causes ectopic expression of EGFR targets such as argos, ventral veinless and decapentaplegic and leads to formation of extra vein tissue. In vein cells, EGFR signalling downregulates Cic protein levels in the nucleus and relieves repression of vein-specific genes, whereas intervein cells maintain high levels of Cic throughout larval and pupal development, repressing the expression of vein-specific genes and allowing intervein differentiation. However, regulation of some EGFR targets such as rhomboid appears not to be under direct control of Cic, suggesting that EGFR signalling branches out in the nucleus and controls different targets via distinct mediator factors. Our results support the idea that localised inactivation of transcriptional repressors such as Cic is a rather general mechanism for regulation of target gene expression by the Ras/Raf pathway.
authors.affiliation: University Museum of Zoology, Department of Zoology, University of Cambridge, Downing Street, Cambridge, UK, CB2 3EJ. roch@cict.fr
authors.forename: Fernando
authors.initials: F
authors.lastname: Roch
authors.forename: Gerardo
authors.initials: G
authors.lastname: Jiménez
authors.forename: Jordi
authors.initials: J
authors.lastname: Casanova
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins; D066246:ErbB Receptors / Q000378:metabolism*; D017344:Genes, Insect; D024002:HMGB Proteins; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014921:Wings, Animal / Q000254:growth & development; D018631:ras Proteins / Q000378:metabolism
chemical_list: C095994:BWK protein, Drosophila; D029721:Drosophila Proteins; D024002:HMGB Proteins; D006609:High Mobility Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C404284:cic protein, Drosophila; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins