EGF receptor signalling protects smooth-cuticle cells from apoptosis during Drosophila ventral epidermis development

Sinisa Urban, Gemma Brown, Matthew Freeman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1835-1845
Number of pages11
JournalDevelopment
Volume131
Issue number8
DOIs
StatePublished - Apr 1 2004

Keywords

  • Apoptosis
  • Cuticle
  • Denticle belt fusion
  • EGF receptor
  • Epidermis
  • Intramembrane proteolysis
  • Pointed
  • Rhomboid
  • Spitz group

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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