The mir-279/996 cluster represses receptor tyrosine kinase signaling to determine cell fates in the Drosophila eye

Development. 2018 Apr 9;145(7):dev159053. doi: 10.1242/dev.159053.

Abstract

Photoreceptors in the crystalline Drosophila eye are recruited by receptor tyrosine kinase (RTK)/Ras signaling mediated by Epidermal growth factor receptor (EGFR) and the Sevenless (Sev) receptor. Analyses of an allelic deletion series of the mir-279/996 locus, along with a panel of modified genomic rescue transgenes, show that Drosophila eye patterning depends on both miRNAs. Transcriptional reporter and activity sensor transgenes reveal expression and function of miR-279/996 in non-neural cells of the developing eye. Moreover, mir-279/996 mutants exhibit substantial numbers of ectopic photoreceptors, particularly of R7, and cone cell loss. These miRNAs restrict RTK signaling in the eye, since mir-279/996 nulls are dominantly suppressed by positive components of the EGFR pathway and enhanced by heterozygosity for an EGFR repressor. miR-279/996 limit photoreceptor recruitment by targeting multiple positive RTK/Ras signaling components that promote photoreceptor/R7 specification. Strikingly, deletion of mir-279/996 sufficiently derepresses RTK/Ras signaling so as to rescue a population of R7 cells in R7-specific RTK null mutants boss and sev, which otherwise completely lack this cell fate. Altogether, we reveal a rare setting of developmental cell specification that involves substantial miRNA control.

Keywords: Drosophila; MicroRNA; R7 photoreceptor; RTK signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Drosophila / embryology
  • Drosophila / metabolism*
  • Drosophila Proteins / metabolism
  • Eye / embryology
  • Eye / metabolism*
  • Eye Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Immunohistochemistry
  • MicroRNAs / metabolism*
  • Organogenesis / genetics
  • Photoreceptor Cells, Invertebrate / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Eye Proteins
  • MIRN279 microRNA, Drosophila
  • MIRN996 microRNA, Drosophila
  • MicroRNAs
  • Receptor Protein-Tyrosine Kinases