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Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish

To help understand the elusive mechanisms of zebrafish sex determination, we studied the genetic machinery regulating production and breakdown of retinoic acid (RA) during the onset of meiosis in gonadogenesis. Results uncovered unexpected mechanistic differences between zebrafish and mammals. Conse...

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Autores principales: Rodríguez-Marí, Adriana, Cañestro, Cristian, BreMiller, Ruth A., Catchen, Julian M., Yan, Yi-Lin, Postlethwait, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769385/
https://www.ncbi.nlm.nih.gov/pubmed/24040125
http://dx.doi.org/10.1371/journal.pone.0073951
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author Rodríguez-Marí, Adriana
Cañestro, Cristian
BreMiller, Ruth A.
Catchen, Julian M.
Yan, Yi-Lin
Postlethwait, John H.
author_facet Rodríguez-Marí, Adriana
Cañestro, Cristian
BreMiller, Ruth A.
Catchen, Julian M.
Yan, Yi-Lin
Postlethwait, John H.
author_sort Rodríguez-Marí, Adriana
collection PubMed
description To help understand the elusive mechanisms of zebrafish sex determination, we studied the genetic machinery regulating production and breakdown of retinoic acid (RA) during the onset of meiosis in gonadogenesis. Results uncovered unexpected mechanistic differences between zebrafish and mammals. Conserved synteny and expression analyses revealed that cyp26a1 in zebrafish and its paralog Cyp26b1 in tetrapods independently became the primary genes encoding enzymes available for gonadal RA-degradation, showing lineage-specific subfunctionalization of vertebrate genome duplication (VGD) paralogs. Experiments showed that zebrafish express aldh1a2, which encodes an RA-synthesizing enzyme, in the gonad rather than in the mesonephros as in mouse. Germ cells in bipotential gonads of all zebrafish analyzed were labeled by the early meiotic marker sycp3, suggesting that in zebrafish, the onset of meiosis is not sexually dimorphic as it is in mouse and is independent of Stra8, which is required in mouse but was lost in teleosts. Analysis of dead-end knockdown zebrafish depleted of germ cells revealed the germ cell-independent onset and maintenance of gonadal aldh1a2 and cyp26a1 expression. After meiosis initiated, somatic cell expression of cyp26a1 became sexually dimorphic: up-regulated in testes but not ovaries. Meiotic germ cells expressing the synaptonemal complex gene sycp3 occupied islands of somatic cells that lacked cyp26a1 expression, as predicted by the hypothesis that Cyp26a1 acts as a meiosis-inhibiting factor. Consistent with this hypothesis, females up-regulated cyp26a1 in oocytes that entered prophase-I meiotic arrest, and down-regulated cyp26a1 in oocytes resuming meiosis. Co-expression of cyp26a1 and the pluripotent germ cell stem cell marker pou5f1(oct4) in meiotically arrested oocytes was consistent with roles in mouse to promote germ cell survival and to prevent apoptosis, mechanisms that are central for tipping the sexual fate of gonads towards the female pathway in zebrafish.
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spelling pubmed-37693852013-09-13 Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish Rodríguez-Marí, Adriana Cañestro, Cristian BreMiller, Ruth A. Catchen, Julian M. Yan, Yi-Lin Postlethwait, John H. PLoS One Research Article To help understand the elusive mechanisms of zebrafish sex determination, we studied the genetic machinery regulating production and breakdown of retinoic acid (RA) during the onset of meiosis in gonadogenesis. Results uncovered unexpected mechanistic differences between zebrafish and mammals. Conserved synteny and expression analyses revealed that cyp26a1 in zebrafish and its paralog Cyp26b1 in tetrapods independently became the primary genes encoding enzymes available for gonadal RA-degradation, showing lineage-specific subfunctionalization of vertebrate genome duplication (VGD) paralogs. Experiments showed that zebrafish express aldh1a2, which encodes an RA-synthesizing enzyme, in the gonad rather than in the mesonephros as in mouse. Germ cells in bipotential gonads of all zebrafish analyzed were labeled by the early meiotic marker sycp3, suggesting that in zebrafish, the onset of meiosis is not sexually dimorphic as it is in mouse and is independent of Stra8, which is required in mouse but was lost in teleosts. Analysis of dead-end knockdown zebrafish depleted of germ cells revealed the germ cell-independent onset and maintenance of gonadal aldh1a2 and cyp26a1 expression. After meiosis initiated, somatic cell expression of cyp26a1 became sexually dimorphic: up-regulated in testes but not ovaries. Meiotic germ cells expressing the synaptonemal complex gene sycp3 occupied islands of somatic cells that lacked cyp26a1 expression, as predicted by the hypothesis that Cyp26a1 acts as a meiosis-inhibiting factor. Consistent with this hypothesis, females up-regulated cyp26a1 in oocytes that entered prophase-I meiotic arrest, and down-regulated cyp26a1 in oocytes resuming meiosis. Co-expression of cyp26a1 and the pluripotent germ cell stem cell marker pou5f1(oct4) in meiotically arrested oocytes was consistent with roles in mouse to promote germ cell survival and to prevent apoptosis, mechanisms that are central for tipping the sexual fate of gonads towards the female pathway in zebrafish. Public Library of Science 2013-09-10 /pmc/articles/PMC3769385/ /pubmed/24040125 http://dx.doi.org/10.1371/journal.pone.0073951 Text en © 2013 Rodríguez-Marí 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rodríguez-Marí, Adriana
Cañestro, Cristian
BreMiller, Ruth A.
Catchen, Julian M.
Yan, Yi-Lin
Postlethwait, John H.
Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish
title Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish
title_full Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish
title_fullStr Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish
title_full_unstemmed Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish
title_short Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish
title_sort retinoic acid metabolic genes, meiosis, and gonadal sex differentiation in zebrafish
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769385/
https://www.ncbi.nlm.nih.gov/pubmed/24040125
http://dx.doi.org/10.1371/journal.pone.0073951
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