Foxl2 functions in sex determination and histogenesis throughout mouse ovary development, analyzed by Affymetrix arrays
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE12905 | GEO | 2009/06/24
SECONDARY ACCESSION(S): PRJNA114259
REPOSITORIES: GEO
Similar Datasets
Project description:Partial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women. In animal models, Foxl2 is required for maintenance, and possibly induction, of female sex determination independently of other critical genes, i.e., Rspo1 and Wnt4. Here we report expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit, to identify ovarian targets of Foxl2 that, along with some testis genes, were dysregulated during embryonic development. Loss of one copy of Foxl2 revealed strong gene dosage sensitivity, with molecular anomalies that were milder but resembled ovaries lacking both Foxl2 alleles. Furthermore, a Foxl2 transgene disrupted embryonic testis differentiation and increased the levels of key female markers. The results, including a comprehensive principal component analysis of published microarray datasets 1) support the proposal of dose-dependent Foxl2 function and anti-testis action throughout ovary differentiation; and 2) identify candidate genes for a role in sex determination independent of FOXL2 (notably, the transcription factor, ZBTB7C) and in the generation of the ovarian reserve downstream of it (e.g., the cadherin-domain protein CLSTN2, or the sphingomyelin synthase, SGMS2). The gene inventory provides a framework to analyze the genetic bases of ovarian development and female fertility. Keywords: reference design Comparison of Foxl2+/+,+/- and -/- whole ovaries at 2 timepoints delineating follicle formation
2010-05-17 | E-GEOD-12942 | biostudies-arrayexpress
Project description:Partial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women. In animal models, Foxl2 is required for maintenance, and possibly induction, of female sex determination independently of other critical genes, i.e., Rspo1 and Wnt4. Here we report expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit, to identify ovarian targets of Foxl2 that, along with some testis genes, were dysregulated during embryonic development. Loss of one copy of Foxl2 revealed strong gene dosage sensitivity, with molecular anomalies that were milder but resembled ovaries lacking both Foxl2 alleles. Furthermore, a Foxl2 transgene disrupted embryonic testis differentiation and increased the levels of key female markers. The results, including a comprehensive principal component analysis of published microarray datasets 1) support the proposal of dose-dependent Foxl2 function and anti-testis action throughout ovary differentiation; and 2) identify candidate genes for a role in sex determination independent of FOXL2 (notably, the transcription factor, ZBTB7C) and in the generation of the ovarian reserve downstream of it (e.g., the cadherin-domain protein CLSTN2, or the sphingomyelin synthase, SGMS2). The gene inventory provides a framework to analyze the genetic bases of ovarian development and female fertility. Keywords: reference design
2009-06-24 | GSE12942 | GEO
Project description:Comparison of Foxl2-null ovaries to wildtype ovaries, ovaries lacking Wnt4 or Kit, or testes, throughout mouse development. The goal of this study was to identify early Foxl2 target genes as well as other ovarian, anti-testis genes that may act independently of Foxl2. Experiment Overall Design: We studied 43 samples over 15 conditions to cover a wide range of wiltype and pathological states showing highly divergent alterations of cell type composition. This was meant to identify the most specific, cell context-independent targets of Foxl2.
2009-07-05 | E-GEOD-12905 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE12905: Foxl2 functions in sex determination and histogenesis throughout mouse ovary development, analyzed by Affymetrix arrays GSE12942: Foxl2 functions in sex determination and histogenesis throughout mouse ovary development, analyzed by Agilent arrays Refer to individual Series
2010-05-17 | E-GEOD-12989 | biostudies-arrayexpress
Project description:We discovered that expression of the transcription factor RUNX1 is enriched in the fetal ovary in various vertebrate species. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. To understand the function of Runx1 during fetal development of the ovary, we ablated Runx1 specifically in the somatic cell lineage of the fetal ovaries using Sf1-Cre . We compared ovarian differentiation in wild type, Runx1 and Foxl2 single knockouts, and Runx1/Foxl2 double knockout ovaries. Transcriptome comparisons of newborn ovaries revealed that loss of Runx1 or Foxl2 affected a similar set of genes: 41% of the genes affected by the loss of Runx1 were also changed by the loss of Foxl2. Despite these transcriptomic changes, granulosa cell identity was maintained during fetal life in both Runx1 or Foxl2 single knockout ovaries. However, the combined loss of Runx1/Foxl2 resulted in masculinization of the ovaries during fetal life. To further characterize the impacts of the combined loss of Runx1 and Foxl2 on ovarian differentiation, we compared the transcriptome of Runx1/Foxl2 DKO newborn ovaries with the transcriptomes of control, Runx1, or Foxl2 single KO ovaries.
2019-07-17 | GSE129038 | GEO
Project description:Foxl2 is a forkhead transcription factor expressed only in the female, but not in the male gonad. We have created mice homozygous mutant for the Foxl2 gene (KO) as well as mice carrying a conditional mutant Foxl2 allele (floxed). The expression profiles of conventional Foxl2 knockout and wildtype ovaries were compared at P3, using the Affy Mouse Genome 430 2.0 Array. Adult wildtype and conditional mutant (Foxl2 floxed x RosaCre-EBD treated with tamoxifen) ovaries were compared to adult wildtype testes using the Affymetrix Mouse Gene 1.0 ST Array. Both experiments (KO/WT P3 and Mutant/WT/Testis Adult were also compared to each other.)
2010-01-01 | GSE16853 | GEO
Project description:Sex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian granulosa cells or testicular Sertoli cells. This process of fate specification hinges on a balance of transcriptional control. We discovered that the transcription factor RUNX1 is enriched in the fetal ovary in rainbow trout, turtle, mouse, and human. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity, and combined loss of RUNX1 and FOXL2 results in masculinization of the fetal ovaries. To determine whether interplay between RUNX1 and FOXL2 occurs at the chromatin level, we performed genome-wide analysis of RUNX1 chromatin occupancy in E14.5 ovaries. The top de novo motif identified in RUNX1 ChIP-seq matched the RUNX motif. We found that RUNX1 chromatin occupancy was partially overlapping with FOXL2 chromatin occupancy in fetal ovaries.
2019-04-02 | GSE128767 | GEO
Project description:BackgroundPartial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women. In animal models, Foxl2 is required for maintenance, and possibly induction, of female sex determination independently of other critical genes, e.g., Rspo1. Here we report expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit.ResultsFollowing Foxl2 loss, early testis genes (including Inhbb, Dhh, and Sox9) and several novel ovarian genes were consistently dysregulated during embryonic development. In the absence of Foxl2, expression changes affecting a large fraction of pathways were opposite those observed in Wnt4-null ovaries, reinforcing the notion that these genes have complementary actions in ovary development. Loss of one copy of Foxl2 revealed strong gene dosage sensitivity, with molecular anomalies that were milder but resembled ovaries lacking both Foxl2 alleles. Furthermore, a Foxl2 transgene disrupted embryonic testis differentiation and increased the levels of key female markers.ConclusionThe results, including a comprehensive principal component analysis, 1) support the proposal of dose-dependent Foxl2 function and anti-testis action throughout ovary differentiation; and 2) identify candidate genes for roles in sex determination independent of FOXL2 (e.g., the transcription factors IRX3 and ZBTB7C) and in the generation of the ovarian reserve downstream of FOXL2 (e.g., the cadherin-domain protein CLSTN2 and the sphingomyelin synthase SGMS2). The gene inventory is a first step toward the identification of the full range of pathways with partly autonomous roles in ovary development, and thus provides a framework to analyze the genetic bases of female fertility.
| S-EPMC2711087 | biostudies-literature
Project description:Gonad somatic cells acquire sex-specific fates during sex determination. In XX gonad, a subset of somatic cells expresses Foxl2 after sex determination which are considered as the progenitor of granulosa cells. However, whether these cells also contribute to other cell type at later developmental stage is unknown. In the present study, the cell fate of Foxl2-expressing cells in fetal ovaries was analyzed by lineage tracing and signal-cell transcriptomics. We found that Foxl2-expressing cells gave rise to three cell types at later developmental stage, including granulosa cells, theca-interstitial cells, and stromal cells. Series single-cell RNA sequencing revealed that Foxl2-positive cells were divided into two clusters at P0. One group further differentiated into granulosa cells and theca cells at P14. Another group was classified as stromal cell lineage, then a small portion of them further differentiated into 3β-HSD-positive interstitial cells. We also found that interstitial cells were CYP17a1-positive, whereas theca cells did express this gene. Our data provide an important resource, at single-cell resolution, for better understanding somatic cell differentiation in ovary development.
2022-11-22 | GSE163879 | GEO
Project description:The identity of the gonads is determined by which fate, ovarian granulosa cell or testicular Sertoli cell, the bipotential somatic cell precursors choose to follow. In most vertebrates, the fate of granulosa cells is controlled by a conserved regulator FOXL2. To understand how FOXL2 elicits its fate-determining action, we performed genome-wide analysis of FOXL2 chromatin occupancy in fetal ovaries. Combining genome-wide analysis of FOXL2 binding in the fetal ovary with transcriptomic analyses of Foxl2 gain-of-function and Foxl2 loss-of-function models, we identified potential pathways responsible for the feminizing action of FOXL2. Finally, comparison of FOXL2 genome-wide occupancy in the fetal ovary with testis-determining factor SOX9 genome-wide occupancy in the fetal testis revealed extensive overlaps, implying that antagonistic signals between FOXL2 and SOX9 occur at the chromatin level.
2019-03-21 | GSE110093 | GEO