RSPO1/β-Catenin Signaling Pathway Regulates Oogonia Differentiation and Entry into Meiosis in the Mouse Fetal Ovary
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{"title"=>"RSPO1/β-Catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary", "type"=>"journal", "authors"=>[{"first_name"=>"Anne Amandine", "last_name"=>"Chassot", "scopus_author_id"=>"6602932553"}, {"first_name"=>"Elodie P.", "last_name"=>"Gregoire", "scopus_author_id"=>"24076101500"}, {"first_name"=>"Rowena", "last_name"=>"Lavery", "scopus_author_id"=>"25640156800"}, {"first_name"=>"Makoto M.", "last_name"=>"Taketo", "scopus_author_id"=>"7004878460"}, {"first_name"=>"Dirk G.", "last_name"=>"de Rooij", "scopus_author_id"=>"7007029491"}, {"first_name"=>"Ian R.", "last_name"=>"Adams", "scopus_author_id"=>"7004323637"}, {"first_name"=>"Marie Christine", "last_name"=>"Chaboissier", "scopus_author_id"=>"6701908832"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"362681550", "doi"=>"10.1371/journal.pone.0025641", "sgr"=>"80053451837", "scopus"=>"2-s2.0-80053451837", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"21991325"}, "id"=>"a90d265d-1ccd-3dfe-8682-1ffba139f942", "abstract"=>"Differentiation of germ cells into male gonocytes or female oocytes is a central event in sexual reproduction. Proliferation and differentiation of fetal germ cells depend on the sex of the embryo. In male mouse embryos, germ cell proliferation is regulated by the RNA helicase Mouse Vasa homolog gene and factors synthesized by the somatic Sertoli cells promote gonocyte differentiation. In the female, ovarian differentiation requires activation of the WNT/β-catenin signaling pathway in the somatic cells by the secreted protein RSPO1. Using mouse models, we now show that Rspo1 also activates the WNT/β-catenin signaling pathway in germ cells. In XX Rspo1(-/-) gonads, germ cell proliferation, expression of the early meiotic marker Stra8, and entry into meiosis are all impaired. In these gonads, impaired entry into meiosis and germ cell sex reversal occur prior to detectable Sertoli cell differentiation, suggesting that β-catenin signaling acts within the germ cells to promote oogonial differentiation and entry into meiosis. Our results demonstrate that RSPO1/β-catenin signaling is involved in meiosis in fetal germ cells and contributes to the cellular decision of germ cells to differentiate into oocyte or sperm.", "link"=>"http://www.mendeley.com/research/rspo1%CE%B2catenin-signaling-pathway-regulates-oogonia-differentiation-entry-meiosis-mouse-fetal-ovary", "reader_count"=>38, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>31, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>31}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Iran"=>1, "United States"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/368217", "https://ndownloader.figshare.com/files/368254"], "description"=>"<div><p>Differentiation of germ cells into male gonocytes or female oocytes is a central event in sexual reproduction. Proliferation and differentiation of fetal germ cells depend on the sex of the embryo. In male mouse embryos, germ cell proliferation is regulated by the RNA helicase <em>Mouse Vasa homolog</em> gene and factors synthesized by the somatic Sertoli cells promote gonocyte differentiation. In the female, ovarian differentiation requires activation of the WNT/<b>β</b>-catenin signaling pathway in the somatic cells by the secreted protein RSPO1. Using mouse models, we now show that <em>Rspo1</em> also activates the WNT/β-catenin signaling pathway in germ cells. In XX <em>Rspo1<sup>−/−</sup></em> gonads, germ cell proliferation, expression of the early meiotic marker <em>Stra8</em>, and entry into meiosis are all impaired. In these gonads, impaired entry into meiosis and germ cell sex reversal occur prior to detectable Sertoli cell differentiation, suggesting that β-catenin signaling acts within the germ cells to promote oogonial differentiation and entry into meiosis. Our results demonstrate that RSPO1/β-catenin signaling is involved in meiosis in fetal germ cells and contributes to the cellular decision of germ cells to differentiate into oocyte or sperm.</p> </div>", "links"=>[], "tags"=>["signaling", "pathway", "regulates", "oogonia", "differentiation", "meiosis", "fetal", "ovary"], "article_id"=>132760, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.s001", "https://dx.doi.org/10.1371/journal.pone.0025641.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/RSPO1_Catenin_Signaling_Pathway_Regulates_Oogonia_Differentiation_and_Entry_into_Meiosis_in_the_Mouse_Fetal_Ovary/132760", "title"=>"RSPO1/β-Catenin Signaling Pathway Regulates Oogonia Differentiation and Entry into Meiosis in the Mouse Fetal Ovary", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-10-03 00:46:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/728576"], "description"=>"<p>A- Reduction of germ cell proliferation in XX <i>Rspo1</i> mutant gonads. Immunodetection of the proliferating germ cells with BrdU and MVH (upper panel), and the apoptotic germ cells with TUNEL and MVH (middle panel), in XY and XX <i>Rspo<sup>+/−</sup></i>, and XX <i>Rspo1<sup>−/−</sup></i> gonads at E12.5 gonads. DAPI (blue): nuclei. Inset middle panel: positive control for TUNEL. Histograms: Percentage of proliferating germ cells or apoptotic germ cells in XY, XX <i>Rspo1<sup>+/−</sup></i> and <i>Rspo1<sup>−/−</sup></i> gonads at E12.5. Bars represent mean+1 SEM, n = 24 sections of each genotype. B- Ablation of <i>Rspo1</i> does not trigger germ cell apopotosis. Quantification of germ cell number and germ cell apoptosis in XX <i>Rspo1<sup>+/−</sup></i> and <i>Rspo1<sup>−/−</sup></i> gonads at E14.5 and E16.5. Bars represent mean+1 SEM, n = 24 sections of each genotype.</p>", "links"=>[], "tags"=>["xx", "germ", "cells"], "article_id"=>398928, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rspo1_promotes_XX_germ_cells_proliferation_/398928", "title"=>"<i>Rspo1</i> promotes XX germ cells proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 02:28:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/728756"], "description"=>"<p>Upper panel: <i>Oct4</i> expression is maintained in XX <i>Rspo1</i> mutant gonads. <i>Oct4</i> whole-mount <i>in situ</i> hybridization at E14.5 in XY, XX control and XX <i>Rspo1<sup>−/−</sup></i> fetal gonads. Middle panels: Downregulation of meiotic markers in XX <i>Rspo1</i> mutant gonads. Immunodetection of SCP3 in E14.5 gonads and of γH2AX and MVH in E16.5 gonads. DAPI (blue): nuclei. Lower panel: Quantification of meiotic germ cells in XX <i>Rspo1<sup>+/−</sup></i> and <i>Rspo1<sup>−/−</sup></i> gonads at E14.5 (SCP3) and E16.5 (γH2AX). Bars represent mean+1 SEM, n = 15 sections of each genotype.</p>", "links"=>[], "tags"=>["xx", "germ", "cells"], "article_id"=>399109, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rspo1_promotes_XX_germ_cells_meiosis_/399109", "title"=>"<i>Rspo1</i> promotes XX germ cells meiosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 02:31:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/728910"], "description"=>"<p>A- Quantitative RT-PCR analysis of <i>Stra8</i>, <i>Cyp26b1</i>, <i>RARα</i> and <i>RARβ</i> expression in E12.5 XY control, XX control, and <i>Rspo1<sup>−/−</sup></i> gonads, using <i>Mvh</i> (for <i>Stra8</i> qPCR) or <i>Hprt</i> (for other qPCR) as the normalization control. Bars represent mean+1 SEM, n = 8 individual embryos. B- <i>In situ</i> hybridizations at E14.5 in XY and XX control and XX <i>Rspo1<sup>−/−</sup></i> gonads for <i>Stra8</i> and <i>Cyp26b1</i>. C- <i>In situ</i> hybridizations on sections of the same XX <i>Rspo1<sup>−/−</sup></i> gonad for <i>Oct4</i> and <i>Stra8</i> at E14.5.</p>", "links"=>[], "tags"=>["induction"], "article_id"=>399271, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rspo1_is_involved_in_induction_of_Stra8_expression_/399271", "title"=>"<i>Rspo1</i> is involved in induction of <i>Stra8</i> expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 02:34:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/729116"], "description"=>"<p>A- <i>In situ</i> hybridizations at E14.5 in XY and XX control and XX <i>Rspo1<sup>−/−</sup></i> gonads for <i>Nanos2</i>. Histograms: Quantitative RT-PCR analysis of <i>Nanos2</i>, <i>Dnmt3L</i> and <i>Tdrd5</i> expression in E14.5 XY control, XX control and <i>Rspo1<sup>−/−</sup></i> gonads, using <i>Hprt</i> as the normalization control. Bars represent mean+1 SEM, n = 8 individual embryos. B- Haematoxylin & Eosin staining of gonadic sections of XY, XX <i>Rspo1<sup>+/−</sup></i> and XX <i>Rspo1<sup>−/−</sup></i> gonads at E16.5. Meiotic oogonia are indicated by arrows GO/G1 quiescent gonocytes are indicated by arrowheads.</p>", "links"=>[], "tags"=>["gonocyte", "markers", "xx", "mutant"], "article_id"=>399465, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Up_regulation_of_of_gonocyte_markers_in_XX_Rspo1_mutant_gonads_/399465", "title"=>"Up-regulation of of gonocyte markers in XX <i>Rspo1</i> mutant gonads.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 02:37:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/729313"], "description"=>"<p>A- Lack of Sertoli cell differentiation at E14.5 in XX <i>Rspo1</i> mutant gonads. <i>In situ</i> hybridizations of <i>Sox9</i> and <i>Pgds</i> in E14.5 XY and XX control and XX <i>Rspo1<sup>−/−</sup></i> gonads. Right panels: Quantitative RT-PCR analysis of <i>Sox9</i> and <i>Pgds</i>, using <i>Hprt</i> as the normalization control. Bars represent mean+1 SEM, n = 8 individual embryos. B- <i>Fgf9</i> is not significantly expressed at E11.5 and E12.5 in XX <i>Rspo1</i> mutant gonads. Upper panels: Quantitative RT-PCR analysis of <i>Fgf9</i> at E11.5, E12.5 and E14.5 using <i>Hprt</i> as the normalization control. NS: Not significant. Bars represent mean+1 SEM, n = 8 individual embryos. Lower panels: <i>In situ</i> hybridizations of <i>Fgf9</i> (E12.5 and E14.5) in XY and XX control and XX <i>Rspo1<sup>−/−</sup></i> gonads.</p>", "links"=>[], "tags"=>["reversal", "caused", "sertoli", "factors", "xx", "mutant"], "article_id"=>399662, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Germ_cell_sex_reversal_is_not_caused_by_Sertoli_cell_factors_in_XX_Rspo1_mutant_gonads_/399662", "title"=>"Germ cell sex reversal is not caused by Sertoli cell factors in XX <i>Rspo1</i> mutant gonads.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 02:41:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/729491"], "description"=>"<p>A- Stabilization of β-catenin in XX germ cells is mediated by <i>Rspo1</i>. Active β-catenin (red) and MVH immunostaining (germ cells, green) in XY, XX <i>Rspo1<sup>+/−</sup></i> and <i>Rspo1<sup>−/−</sup></i> gonads at E14.5. DAPI (blue): nuclei. Arrowheads: nuclear β-catenin staining. B- Effectors of the WNT/β-catenin signaling pathway are expressed in XX germ cells. Quantitative RT-PCR analysis of <i>Axin2</i>, <i>Lef1</i>, <i>LRP6</i> expression in E13.5 germ cells (XX and XY <i>Oct4</i>-positive cells) and somatic cells (XX and XY <i>Oct4</i>-negative cells), using respectively <i>Hprt</i> as the normalization control. Bars represent mean+1 SEM, n = 3 individual experiments. C- Expression of <i>Axin2</i>, a target of β-catenin in XX germ cells. X-Gal staining (AXIN2) (blue) and MVH immunostaining (germ cells, red) in XY <i>Axin2<sup>+/LacZ</sup></i>, XX <i>Axin2<sup>+/LacZ</sup></i> and XX <i>Axin2<sup>+/LacZ</sup></i>; <i>Rspo1<sup>−/−</sup></i> gonads at E12.5. Arrowheads: germ cells. G: gonad. X-Gal staining (AXIN2) (blue) and MVH immunostaining (germ cells, green) on isolated germ cells from XY <i>Axin2<sup>+/LacZ</sup></i> and XX <i>Axin2<sup>+/LacZ</sup></i> gonads at E12.5. Arrowheads: germ cells, arrows: somatic cells.</p>", "links"=>[], "tags"=>["activates", "signaling", "pathway", "xx", "germ"], "article_id"=>399834, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rspo1_activates_catenin_signaling_pathway_in_XX_germ_cells_/399834", "title"=>"<i>Rspo1</i> activates β-catenin signaling pathway in XX germ cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 02:43:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/729638"], "description"=>"<p>A- Upper panel: Immunodetection of active β-catenin and MVH in XY and XX control and XY <i>Catnb<sup>ex3/+</sup></i>; <i>TNAP:Cre<sup>Tr</sup></i> gonads at E14.5. Middle panel: Immunodetection of the proliferating germ cells with BrdU and MVH in XY and XX control, and XY <i>Catnb<sup>ex3/+</sup></i>; <i>TNAP:Cre<sup>Tr</sup></i> gonads at E14.5. DAPI (blue): nuclei. Histograms: Percentage of BrdU-positive germ cells in XY and XX control, and XY <i>Catnb<sup>ex3/+</sup></i>; <i>TNAP:Cre<sup>Tr</sup></i> gonads at E14.5. Bars represent mean+1 SEM, n = 24 sections of each genotype. Lower panel: Haematoxylin & Eosin staining of E15.5 gonadic sections from XY and XX wild type gonads and XY <i>Catnb<sup>ex3/+</sup></i>; <i>TNAP:Cre<sup>Tr</sup></i> gonads. Arrowheads: XY quiescent gonocytes, arrows: meiotic germ cells, dashed arrows: mitotic germ cells, thin arrowhead: putative early meiotic germ cell. Histogram: Quantitative RT-PCR analysis of <i>Stra8</i> at E15.5 using <i>Mvh</i> as the normalization control. Bars represent mean+1 SEM, n = 8 individual embryos. B- Upper panel: Immunostaining of FOXL2 (green) and E-Cadherin (germ cells, red) in XY and XX control, and XY <i>Catnb<sup>ex3/+</sup></i>; <i>TNAP:Cre<sup>Tr</sup></i> gonads at E14.5. The white star indicates fluorescent blood cells within the coelomic vessel of the XY gonads. Lower panel: Immunodetection of the Sertoli cell marker SDMG1 in the same gonads. DAPI (blue): nuclei.</p>", "links"=>[], "tags"=>["xy", "germ", "proliferation", "fetal"], "article_id"=>399982, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Activation_of_946_catenin_promotes_XY_germ_cell_proliferation_in_fetal_gonads_/399982", "title"=>"Activation of β-catenin promotes XY germ cell proliferation in fetal gonads.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 02:46:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/729816"], "description"=>"<p>A- Proliferation is not impaired in XX <i>Catnb <sup>flox/flox</sup></i>; <i>Sf1:Cre<sup>Tr</sup></i> gonads. Immunodetection of the proliferating germ cells with BrdU (green) and MVH (red) in XY, XX control and XX <i>Catnb <sup>flox/flox</sup></i>; <i>Sf1:Cre<sup>Tr</sup></i> gonads at E12.5. DAPI (blue): nuclei. Histograms: Percentage of BrdU-positive germ cells in XY, XX control and XX <i>Catnb <sup>flox/flox</sup></i>; <i>Sf1:Cre<sup>Tr</sup></i> gonads at E12.5. Bars represent mean+1 SEM, n = 24 sections of each genotype. B- Meiosis in not hampered in XX<i>Catnb <sup>flox/flox</sup></i>; <i>Sf1:Cre<sup>Tr</sup></i> gonads. Haematoxylin & Eosin staining of sections from E17.5 XY, XX control and XX <i>Catnb <sup>flox/flox</sup></i>; <i>Sf1:Cre<sup>Tr</sup></i> gonads. Arrowheads: gonocytes, arrows: meiotic germ cells, dotted arrows: apoptotic germ cells. <i>Histograms</i>: Percentage of apoptotic germ cells versus total germ cells after TUNEL staining in XY, XX control gonads and XX <i>Catnb <sup>flox/flox</sup></i>; <i>Sf1:Cre<sup>Tr</sup></i> gonads. Bars represent mean+1 SEM, n = 24 sections of each genotype. C: Immunodetection of SOX9 (red) in XY, XX control gonads and XX <i>Catnb <sup>flox/flox</sup></i>; <i>Sf1:Cre<sup>Tr</sup></i> gonads at E18.5. DAPI (blue) was used to detect nuclei.</p>", "links"=>[], "tags"=>["ablation", "germ"], "article_id"=>400170, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Somatic_ablation_of_946_catenin_does_not_affect_germ_cell_fate_/400170", "title"=>"Somatic ablation of β-catenin does not affect germ cell fate.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 00:02:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/729940"], "description"=>"<p>Male and female fetal germ cells have acquired independent mechanisms to regulate their differentiation. In the fetal testis, <i>Mvh</i> is required to promote germ cell proliferation. FGF9 secreted by Sertoli cells promotes germ cell survival and may inhibit entry into meiosis. Then <i>Nanos2</i> promotes differentiation into gonocytes and meiosis inhibition. RSPO1 has been shown to be a secreted activator of β-catenin. In fetal ovary, RSPO1/β-catenin signalling pathway promotes germ cell proliferation. Then, in addition to the retinoic acid (RA) signaling pathway, RSPO1 contributes in meiosis entry as a parallel pathway (indicated by the presence of two parallel arrows). RSPO1 promotes <i>Stra8</i> expression and subsequently meiosis initiation. Although we showed that RSPO1 is a direct activator of β-catenin in XX germ cells suggesting that RSPO1 is also acting via β-catenin in this developmental process, the direct inactivation of β-catenin in XX germ cells remains to be done. Yellow-filled circles: undifferentiated germ cells; blue-filled and pink-filled circles: respectively male and female germ cells at the differentiating stage. RA: Retinoic Acid.</p>", "links"=>[], "tags"=>["signals", "germ"], "article_id"=>400289, "categories"=>["Molecular Biology", "Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Anne-Amandine Chassot", "Elodie P. Gregoire", "Rowena Lavery", "Makoto M. Taketo", "Dirk G. de Rooij", "Ian R. Adams", "Marie-Christine Chaboissier"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025641.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Opposing_signals_regulate_germ_cell_sexual_differentiation_/400289", "title"=>"Opposing signals regulate germ cell sexual differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-03 00:04:49"}

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  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
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  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"28", "full-text"=>"29", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"25", "full-text"=>"31", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
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Relative Metric

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