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Chinmo prevents transformer alternative splicing to maintain male sex identity

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Title: Chinmo prevents transformer alternative splicing to maintain male sex identity
Authors: Grmai, L
Hudry, B
Miguel-Aliaga, I
Bach, EA
Item Type: Journal Article
Abstract: Reproduction in sexually dimorphic animals relies on successful gamete production, executed by the germline and aided by somatic support cells. Somatic sex identity in Drosophila is instructed by sex-specific isoforms of the DMRT1 ortholog Doublesex (Dsx). Female-specific expression of Sex-lethal (Sxl) causes alternative splicing of transformer (tra) to the female isoform traF. In turn, TraF alternatively splices dsx to the female isoform dsxF. Loss of the transcriptional repressor Chinmo in male somatic stem cells (CySCs) of the testis causes them to “feminize”, resembling female somatic stem cells in the ovary. This somatic sex transformation causes a collapse of germline differentiation and male infertility. We demonstrate this feminization occurs by transcriptional and post-transcriptional regulation of traF. We find that chinmo-deficient CySCs upregulate tra mRNA as well as transcripts encoding tra-splice factors Virilizer (Vir) and Female lethal (2)d (Fl(2)d). traF splicing in chinmo-deficient CySCs leads to the production of DsxF at the expense of the male isoform DsxM, and both TraF and DsxF are required for CySC sex transformation. Surprisingly, CySC feminization upon loss of chinmo does not require Sxl but does require Vir and Fl(2)d. Consistent with this, we show that both Vir and Fl(2)d are required for tra alternative splicing in the female somatic gonad. Our work reveals the need for transcriptional regulation of tra in adult male stem cells and highlights a previously unobserved Sxl-independent mechanism of traF production in vivo. In sum, transcriptional control of the sex determination hierarchy by Chinmo is critical for sex maintenance in sexually dimorphic tissues and is vital in the preservation of fertility.
Issue Date: 1-Feb-2018
Date of Acceptance: 16-Jan-2018
URI: http://hdl.handle.net/10044/1/60139
DOI: https://dx.doi.org/10.1371/journal.pgen.1007203
ISSN: 1553-7390
Publisher: Public Library of Science (PLoS)
Start Page: 1
End Page: 27
Journal / Book Title: PLoS Genetics
Volume: 14
Issue: 2
Copyright Statement: © 2018 Grmai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/J007110/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
CELL SELF-RENEWAL
DROSOPHILA TESTIS NICHE
CENTRAL-NERVOUS-SYSTEM
STEM-CELLS
DOUBLESEX PROTEINS
REGULATORY ELEMENTS
PRIMARY TRANSCRIPT
JAK/STAT PATHWAY
GENE-EXPRESSION
SOMATIC CONTROL
0604 Genetics
Developmental Biology
Publication Status: Published
Article Number: ARTN e1007203
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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