{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:41:00Z","timestamp":1768506060369,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,21]]},"group-title":"Developmental Biology","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Mitogen-Activated Protein 3 Kinase 1 (MAP3K1) is a dynamic signaling molecule with a plethora of cell-type specific functions, most of which are yet to be understood. Here we describe a role for MAP3K1 in the development of female reproductive tract (FRT). MAP3K1 kinase domain-deficient (\n                  <jats:italic>\n                    Map3k1\n                    <jats:sup>\u0394KD<\/jats:sup>\n                  <\/jats:italic>\n                  ) females exhibit imperforate vagina, labor failure, and infertility. These defects correspond to a shunted M\u00fcllerian duct (MD), the principle precursor of the FRT, in embryos, while they manifest as a contorted caudal vagina with abrogated vaginal-urogenital sinus fusion in neonates. In epithelial cells, MAP3K1 acts through JNK and ERK to activate WNT, yet\n                  <jats:italic>in vivo<\/jats:italic>\n                  MAP3K1 is crucial for WNT activity in mesenchyme associated with the caudal MD. Expression of\n                  <jats:italic>Wnt7b<\/jats:italic>\n                  is high in wild type, but low in\n                  <jats:italic>Map3k1<\/jats:italic>\n                  knockout MD epithelium and MAP3K1-deficient keratinocytes. Correspondingly, conditioned media derived from MAP3K1-competent epithelial cells activate TCF\/Lef-luciferase reporter in fibroblasts, suggesting that MAP3K1-induced factors released from epithelial cells trans-activate WNT signaling in fibroblasts. Our results reveal a temporal-spatial and paracrine MAP3K1-WNT crosstalk contributing to MD caudal elongation and FRT development.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>MAP3K1 deficient female mice exhibit imperforate vagina and infertility<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Loss of MAP3K1 kinase activity impedes M\u00fcllerian duct (MD) caudal elongation and fusion with urogenital sinus (UGS) in embryogenesis<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>The MAP3K1-MAPK pathway up-regulates WNT signaling in epithelial cells<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>MAP3K1 deficiency down-regulates Wnt7b expression in the MD epithelium and prevents WNT activity in mesenchyme of the caudal MD<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2023.04.20.537715","type":"posted-content","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T08:30:14Z","timestamp":1682065814000},"source":"Crossref","is-referenced-by-count":2,"title":["The Role of MAP3K1 in the Development of the Female Reproductive 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