title: EGF receptor signalling protects smooth-cuticle cells from apoptosis during Drosophila ventral epidermis development.
abstract: Patterning of the Drosophila ventral epidermis is a tractable model for understanding the role of signalling pathways in development. Interplay between Wingless and EGFR signalling determines the segmentally repeated pattern of alternating denticle belts and smooth cuticle: spitz group genes, which encode factors that stimulate EGFR signalling, induce the denticle fate, while Wingless signalling antagonizes the effect of EGFR signalling, allowing cells to adopt the smooth-cuticle fate. Medial fusion of denticle belts is also a hallmark of spitz group genes, yet its underlying cause is unknown. We have studied this phenotype and discovered a new function for EGFR signalling in epidermal patterning. Smooth-cuticle cells, which are receiving Wingless signalling, are nevertheless dependent on EGFR signalling for survival. Reducing EGFR signalling results in apoptosis of smooth-cuticle cells between stages 12 and 14, bringing adjacent denticle regions together to result in denticle belt fusions by stage 15. Multiple factors stimulate EGFR signalling to promote smooth-cuticle cell survival: in addition to the spitz group genes, Rhomboid-3/roughoid, but not Rhomboid-2 or -4, and the neuregulin-like ligand Vein also function in survival signalling. Pointed mutants display the lowest frequency of fusions, suggesting that EGFR signalling may inhibit apoptosis primarily at the post-translational level. All ventral epidermal cells therefore require some level of EGFR signalling; high levels specify the denticle fate, while lower levels maintain smooth-cuticle cell survival. This strategy might guard against developmental errors, and may be conserved in mammalian epidermal patterning.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Urban
authors.forename: Gemma
authors.initials: G
authors.lastname: Brown
authors.forename: Matthew
authors.initials: M
authors.lastname: Freeman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor; D004817:Epidermis / Q000002:abnormalities / Q000196:embryology*; D066246:ErbB Receptors / Q000502:physiology*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; C081481:Rho protein, Drosophila; C076026:spi protein, Drosophila; D004815:Epidermal Growth Factor; D066246:ErbB Receptors