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

Abstract

Photoreceptors in the crystalline <i>Drosophila</i> 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 <i>mir-279/996</i> locus, along with a panel of modified genomic rescue transgenes, show that <i>Drosophila</i> 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, <i>mir-279/996</i> mutants exhibit substantial numbers of ectopic photoreceptors, particularly of R7, and cone cell loss. These miRNAs restrict RTK signaling in the eye, since <i>mir-279/996</i> 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 <i>mir-279/996</i> sufficiently derepresses RTK/Ras signaling so as to rescue a population of R7 cells in R7-specific RTK null mutants <i>boss</i> and <i>sev</i>, which otherwise completely lack this cell fate. Altogether, we reveal a rare setting of developmental cell specification that involves substantial miRNA control.