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Chinmo prevents transformer alternative splicing to maintain male sex identity

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 (S...

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Autores principales: Grmai, Lydia, Hudry, Bruno, Miguel-Aliaga, Irene, Bach, Erika A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811060/
https://www.ncbi.nlm.nih.gov/pubmed/29389999
http://dx.doi.org/10.1371/journal.pgen.1007203
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author Grmai, Lydia
Hudry, Bruno
Miguel-Aliaga, Irene
Bach, Erika A.
author_facet Grmai, Lydia
Hudry, Bruno
Miguel-Aliaga, Irene
Bach, Erika A.
author_sort Grmai, Lydia
collection PubMed
description 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 tra(F). In turn, Tra(F) alternatively splices dsx to the female isoform dsx(F). 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 tra(F). 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). tra(F) splicing in chinmo-deficient CySCs leads to the production of Dsx(F) at the expense of the male isoform Dsx(M), and both Tra(F) and Dsx(F) 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 tra(F) 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.
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spelling pubmed-58110602018-02-28 Chinmo prevents transformer alternative splicing to maintain male sex identity Grmai, Lydia Hudry, Bruno Miguel-Aliaga, Irene Bach, Erika A. PLoS Genet Research Article 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 tra(F). In turn, Tra(F) alternatively splices dsx to the female isoform dsx(F). 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 tra(F). 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). tra(F) splicing in chinmo-deficient CySCs leads to the production of Dsx(F) at the expense of the male isoform Dsx(M), and both Tra(F) and Dsx(F) 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 tra(F) 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. Public Library of Science 2018-02-01 /pmc/articles/PMC5811060/ /pubmed/29389999 http://dx.doi.org/10.1371/journal.pgen.1007203 Text en © 2018 Grmai et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Grmai, Lydia
Hudry, Bruno
Miguel-Aliaga, Irene
Bach, Erika A.
Chinmo prevents transformer alternative splicing to maintain male sex identity
title Chinmo prevents transformer alternative splicing to maintain male sex identity
title_full Chinmo prevents transformer alternative splicing to maintain male sex identity
title_fullStr Chinmo prevents transformer alternative splicing to maintain male sex identity
title_full_unstemmed Chinmo prevents transformer alternative splicing to maintain male sex identity
title_short Chinmo prevents transformer alternative splicing to maintain male sex identity
title_sort chinmo prevents transformer alternative splicing to maintain male sex identity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811060/
https://www.ncbi.nlm.nih.gov/pubmed/29389999
http://dx.doi.org/10.1371/journal.pgen.1007203
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