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

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

Author information

1
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York, NY 10065, USA.
2
Program in Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA.
3
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, 701 West 168th Street, New York, NY 10032, USA.
4
Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
5
Department of Biology, Colby College, Waterville, ME 04901, USA.
6
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York, NY 10065, USA laie@mskcc.org.

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

PMID:
29540498
PMCID:
PMC5963866
DOI:
10.1242/dev.159053
[Indexed for MEDLINE]
Free PMC Article

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