The mir-279/996 cluster represses receptor tyrosine kinase signaling to determine cell fates in the Drosophila eye
| Autor: | Yannis Emmanuel Mavromatakis, Cyrus Zhou, Kayla Viets, Andrew Tomlinson, Luis F. de Navas, Joshua Kavaler, Robert J. Johnston, Hong Duan, Eric C. Lai, Kailiang Sun, Fuqu Hu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
education.field_of_study biology fungi Population Cell Repressor Cell fate determination Receptor tyrosine kinase Cell biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure microRNA biology.protein medicine sense organs Epidermal growth factor receptor education Receptor Molecular Biology Developmental Biology |
| Zdroj: | Development. |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.159053 |
| Popis: | Photoreceptors in the crystalline Drosophila eye are recruited by receptor tyrosine kinase (RTK)/Ras signaling, mediated by the Epidermal Growth Factor receptor (EGFR) and Sevenless receptor. Analyses of an allelic deletion series of the mir-279/996 locus, along with a panel of modified genomic rescue transgenes, show that normal 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 de-represses 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 substantially requires miRNA control. |
| Databáze: | OpenAIRE |
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