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Human mutations in\n                      <jats:italic>FOXL2<\/jats:italic>\n                      cause blepharophimosis, ptosis, epicanthus and inversus syndrome (BPES), which can be associated with primary ovarian insufficiency, and is indirectly linked with differences of sex development (DSD). Animal studies have shown the crucial role that\n                      <jats:italic>FOXL2<\/jats:italic>\n                      plays in the development, function, and maintenance of the ovary as well as in sex determination. However, the specific role of\n                      <jats:italic>FOXL2<\/jats:italic>\n                      in early human somatic cell ovarian development is largely unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we utilised CRISPR\/Cas9 genome activation and a previously published in-house 14-day gonadal differentiation protocol to study the role of\n                      <jats:italic>FOXL2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results demonstrate that\n                      <jats:italic>FOXL2<\/jats:italic>\n                      downregulates coelomic epithelial markers\n                      <jats:italic>GATA4<\/jats:italic>\n                      and\n                      <jats:italic>LHX9<\/jats:italic>\n                      , female gonadal markers\n                      <jats:italic>RSPO1<\/jats:italic>\n                      and\n                      <jats:italic>WNT4<\/jats:italic>\n                      , and male gonadal markers\n                      <jats:italic>SOX9<\/jats:italic>\n                      ,\n                      <jats:italic>NR0B1<\/jats:italic>\n                      and\n                      <jats:italic>DHH<\/jats:italic>\n                      . The differentially expressed genes were mostly associated with Kyoto encyclopaedia of genes and genomes (KEGG) pathways relating to cell adhesion molecules and gene ontology (GO) pathways relating to extracellular matrix and junction formation. Furthermore, a comparative analysis with existing single cell RNA sequencing data from human in vivo-derived samples elucidated that\n                      <jats:italic>FOXL2<\/jats:italic>\n                      initiates the downregulation of coelomic epithelial genes\n                      <jats:italic>GATA4<\/jats:italic>\n                      ,\n                      <jats:italic>LHX9<\/jats:italic>\n                      and\n                      <jats:italic>UPK3B<\/jats:italic>\n                      at day 6. By day 8, the genes\n                      <jats:italic>ARX<\/jats:italic>\n                      and\n                      <jats:italic>GATA2<\/jats:italic>\n                      are transiently upregulated by\n                      <jats:italic>FOXL2<\/jats:italic>\n                      induction and then downregulated as the genes\n                      <jats:italic>LGR5<\/jats:italic>\n                      ,\n                      <jats:italic>TSPAN8<\/jats:italic>\n                      ,\n                      <jats:italic>OSR1<\/jats:italic>\n                      and\n                      <jats:italic>TAC1<\/jats:italic>\n                      become upregulated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings suggest that\n                      <jats:italic>FOXL2<\/jats:italic>\n                      facilitates the exit of differentiating cells from the coelomic epithelium and initially drives them towards a transitional identity before progressing into early supporting gonadal-like cells. The findings of this study significantly advance our understanding of normal gonadal development which can be used as a basis to elucidate pathological gonadal development underlying BPES.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12958-025-01377-0","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T04:22:12Z","timestamp":1742271732000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["FOXL2 drives the differentiation of supporting gonadal cells in early ovarian development"],"prefix":"10.1186","volume":"23","author":[{"given":"Laura","family":"Danti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Lundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Nedeczey-Ruzs\u00e1k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Tuuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha S.","family":"Tapanainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"1377_CR1","unstructured":"Tucker EJ. 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