MAP3K1 regulates female reproductive tract development
© 2024. Published by The Company of Biologists Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Disease models & mechanisms - 17(2024), 3 vom: 01. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kimura, Eiki [VerfasserIn] |
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| Links: |
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| Themen: |
EC 2.7.11.25 |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 09.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1242/dmm.050669 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369908538 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Female reproductive tract | |
| 650 | 4 | |a Imperforate vagina | |
| 650 | 4 | |a MAP3K1 | |
| 650 | 4 | |a Müllerian duct | |
| 650 | 4 | |a WNT signaling | |
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| 700 | 1 | |a Xiao, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Christianto, Antonius |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Carreira, Vinicius S |e verfasserin |4 aut | |
| 700 | 1 | |a Bolon, Brad |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Burns, Katherine A |e verfasserin |4 aut | |
| 700 | 1 | |a Biesiada, Jacek |e verfasserin |4 aut | |
| 700 | 1 | |a Medvedovic, Mario |e verfasserin |4 aut | |
| 700 | 1 | |a Puga, Alvaro |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Ying |e verfasserin |4 aut | |
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