Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration.
The androgen receptor (AR) is a nuclear hormone receptor, and its activation through binding to androgens is essential for prostate development, morphogenesis, growth, and tumorigenesis. Although significant efforts have been devoted to understanding the critical role of AR, the cellular properties...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-06-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011756 |
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| author | Yao Mawulikplimi Adzavon Dong-Hoon Lee Alex Hiroto Tae Ju Park Gaeul Chu Yunjeong Kim Kristoffer Nikias Cheong-Wun Kim Dexter Hoi Long Leung Chenmiao Liu Hong Zeng Zijie Sun |
| author_facet | Yao Mawulikplimi Adzavon Dong-Hoon Lee Alex Hiroto Tae Ju Park Gaeul Chu Yunjeong Kim Kristoffer Nikias Cheong-Wun Kim Dexter Hoi Long Leung Chenmiao Liu Hong Zeng Zijie Sun |
| author_sort | Yao Mawulikplimi Adzavon |
| collection | DOAJ |
| description | The androgen receptor (AR) is a nuclear hormone receptor, and its activation through binding to androgens is essential for prostate development, morphogenesis, growth, and tumorigenesis. Although significant efforts have been devoted to understanding the critical role of AR, the cellular properties and functions of the AR-expressing cells acting as prostatic progenitors in controlling prostatic cell differentiation and growth still remain elusive. Additionally, dynamic paracrine interactions between urogenital mesenchyme and epithelia initiated by the AR activation through prostate development are also largely unknown. Recently, we modified the mouse Ar gene locus, which enables us to genetically label AR-expressing cells spatiotemporally and trace them through prostate development, morphogenesis, and growth in combination with a double-fluorescent reporter mouse model. The membrane-bound green fluorescent protein (mGFP)-expressing cells were revealed in both urogenital sinus mesenchyme (UGM) and epithelium (UGE) at embryonic day E18.5 when Tamoxifen was administrated at E13.5 to activate CreER recombinase directed by the endogenous Ar promoter. The AR-expressing cells and their descendants were further detected at postnatal days 10, 35, and 56, and through three cycles of prostatic regeneration by repeated androgen deprivation and replacement. Deletion of β-catenin through the AR-driven CreER in embryonic AR-expressing cells impairs prostate development and morphogenesis. Specifically, altered β-catenin expression results in loss of prostatic glandular cell polarity and activation of Fas death signaling pathways. These lines of experimental evidence demonstrate the biological relevance and significance of this new genetic tool to assess and visualize AR-mediated signaling pathways through prostatic development, growth, and tumorigenesis. |
| format | Article |
| id | doaj-art-285be8e442614747a64c3c9bbed01c39 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-285be8e442614747a64c3c9bbed01c392025-08-20T02:37:41ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-06-01216e101175610.1371/journal.pgen.1011756Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration.Yao Mawulikplimi AdzavonDong-Hoon LeeAlex HirotoTae Ju ParkGaeul ChuYunjeong KimKristoffer NikiasCheong-Wun KimDexter Hoi Long LeungChenmiao LiuHong ZengZijie SunThe androgen receptor (AR) is a nuclear hormone receptor, and its activation through binding to androgens is essential for prostate development, morphogenesis, growth, and tumorigenesis. Although significant efforts have been devoted to understanding the critical role of AR, the cellular properties and functions of the AR-expressing cells acting as prostatic progenitors in controlling prostatic cell differentiation and growth still remain elusive. Additionally, dynamic paracrine interactions between urogenital mesenchyme and epithelia initiated by the AR activation through prostate development are also largely unknown. Recently, we modified the mouse Ar gene locus, which enables us to genetically label AR-expressing cells spatiotemporally and trace them through prostate development, morphogenesis, and growth in combination with a double-fluorescent reporter mouse model. The membrane-bound green fluorescent protein (mGFP)-expressing cells were revealed in both urogenital sinus mesenchyme (UGM) and epithelium (UGE) at embryonic day E18.5 when Tamoxifen was administrated at E13.5 to activate CreER recombinase directed by the endogenous Ar promoter. The AR-expressing cells and their descendants were further detected at postnatal days 10, 35, and 56, and through three cycles of prostatic regeneration by repeated androgen deprivation and replacement. Deletion of β-catenin through the AR-driven CreER in embryonic AR-expressing cells impairs prostate development and morphogenesis. Specifically, altered β-catenin expression results in loss of prostatic glandular cell polarity and activation of Fas death signaling pathways. These lines of experimental evidence demonstrate the biological relevance and significance of this new genetic tool to assess and visualize AR-mediated signaling pathways through prostatic development, growth, and tumorigenesis.https://doi.org/10.1371/journal.pgen.1011756 |
| spellingShingle | Yao Mawulikplimi Adzavon Dong-Hoon Lee Alex Hiroto Tae Ju Park Gaeul Chu Yunjeong Kim Kristoffer Nikias Cheong-Wun Kim Dexter Hoi Long Leung Chenmiao Liu Hong Zeng Zijie Sun Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration. PLoS Genetics |
| title | Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration. |
| title_full | Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration. |
| title_fullStr | Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration. |
| title_full_unstemmed | Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration. |
| title_short | Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration. |
| title_sort | visualizing androgen signaling and assessing its interaction with canonical wnt signaling pathways in prostate development morphogenesis and regeneration |
| url | https://doi.org/10.1371/journal.pgen.1011756 |
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