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Herein, we describe a role for MAP3K1 in female reproductive tract (FRT) development. MAP3K1 kinase domain-deficient female mice exhibited an imperforate vagina, labor failure and infertility. These defects corresponded with shunted M\u00fcllerian ducts (MDs), the embryonic precursors of FRT, that manifested as a contorted caudal vagina and abrogated vaginal\u2013urogenital sinus fusion in neonates. The MAP3K1 kinase domain is required for optimal activation of the Jun-N-terminal kinase (JNK) and cell polarity in the MD epithelium, and for upregulation of WNT signaling in the mesenchyme surrounding the caudal MD. The MAP3K1-deficient epithelial cells and MD epithelium had reduced expression of WNT7B ligands. Correspondingly, conditioned media derived from MAP3K1-competent, but not -deficient, epithelial cells activated a TCF\/Lef-luciferase reporter in fibroblasts. These observations indicate that MAP3K1 regulates MD caudal elongation and FRT development, in part through the induction of paracrine factors in the epithelium that trans-activate WNT signaling in the mesenchyme.<\/jats:p>","DOI":"10.1242\/dmm.050669","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T08:26:49Z","timestamp":1710836809000},"source":"Crossref","is-referenced-by-count":4,"title":["MAP3K1 regulates female reproductive tract development"],"prefix":"10.1242","volume":"17","author":[{"given":"Eiki","family":"Kimura","sequence":"first","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Mongan","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xiao","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius","family":"Christianto","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius S.","family":"Carreira","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Bolon","sequence":"additional","affiliation":[{"name":"GEMpath Inc 2 ., Longmont, CO 80501-1846 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Burns","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Biesiada","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Medvedovic","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Puga","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9532-9527","authenticated-orcid":false,"given":"Ying","family":"Xia","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine 1 Department of Environmental and Public Health Sciences , , Cincinnati, OH 45267-0056 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"2024032810031947400_DMM050669C1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ogc.2009.02.001","article-title":"Disorders of sexual development","volume":"36","author":"Allen","year":"2009","journal-title":"Obstet. 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