The mir-279/996 cluster represses receptor tyrosine kinase signaling to determine cell fates in the Drosophila eye.
Hong DuanLuis F de NavasFuqu HuKailiang SunYannis E MavromatakisKayla VietsCyrus ZhouJoshua KavalerRobert J JohnstonAndrew TomlinsonEric C LaiPublished in: Development (Cambridge, England) (2018)
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.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- cell proliferation
- long non coding rna
- long noncoding rna
- single cell
- advanced non small cell lung cancer
- poor prognosis
- cell fate
- small cell lung cancer
- induced apoptosis
- cell cycle arrest
- mesenchymal stem cells
- cell therapy
- signaling pathway
- binding protein
- transcription factor
- stem cells
- cell death
- dna methylation
- endoplasmic reticulum stress
- copy number