{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kimura E"],"funding":["NICHD NIH HHS","NIEHS NIH HHS","University of Cincinnati","National Institutes of Health","NIH HHS"],"pagination":["dmm050669"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10985838"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(3)"],"pubmed_abstract":["Mitogen-activated protein 3 kinase 1 (MAP3K1) has a plethora of cell type-specific functions not yet fully understood. 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 Müllerian ducts (MDs), the embryonic precursors of FRT, that manifested as a contorted caudal vagina and abrogated vaginal-urogenital 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."],"journal":["Disease models & mechanisms"],"pubmed_title":["MAP3K1 regulates female reproductive tract development."],"pmcid":["PMC10985838"],"funding_grant_id":["R01HD098106","R01 HD098106","R01ES010807","R01 ES010807","P30ES006096","R21ES033342","P30 ES006096","R21 ES033342"],"pubmed_authors":["Xia Y","Biesiada J","Burns KA","Puga A","Mongan M","Bolon B","Wang J","Carreira VS","Medvedovic M","Kimura E","Zhang X","Xiao B","Christianto A"],"additional_accession":[]},"is_claimable":false,"name":"MAP3K1 regulates female reproductive tract development.","description":"Mitogen-activated protein 3 kinase 1 (MAP3K1) has a plethora of cell type-specific functions not yet fully understood. 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 Müllerian ducts (MDs), the embryonic precursors of FRT, that manifested as a contorted caudal vagina and abrogated vaginal-urogenital 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2024-12-04T06:21:42.786Z","creation":"2024-12-04T06:21:42.786Z"},"accession":"S-EPMC10985838","cross_references":{"pubmed":["38501211"],"doi":["10.1242/dmm.050669"]}}