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In this study, Smoothened (Smo), the central transducer of Hedgehog signaling pathway, was characterized in medaka (Oryzias latipes), and its role and underlying mechanisms in the proliferation of spermatogonia were investigated. Smo was highly expressed in spermatogonia. In ex vivo testicular organ culture and a spermatogonial cell line (SG3) derived from medaka mature testis, Smo activation promoted spermatogonia proliferation, while its inhibition induced apoptosis. The expression of glioma-associated oncogene homolog 1 (gli1) and regulator of cell cycle (rgcc) was significantly upregulated in SG3 after Smo activation. Furthermore, Gli1 transcriptionally upregulated the expression of rgcc, and Rgcc overexpression rescued cell apoptosis caused by Smo or Gli1 inhibition. Co-immunoprecipitation assay indicated that Rgcc could interact with cyclin-dependent kinase 1 (Cdk1) to regulate the cell cycle of spermatogonia. Collectively, our study firstly reveals that Smo mediates the proliferation of spermatogonia through Gli1\u2013Rgcc\u2013Cdk1 axis. In addition, Smo and Gli1 are necessary of the survival of spermatogonia. This study deepens our understanding of spermatogonia proliferation and survival at the molecular level, and provides insights into male fertility control and reproductive disease treatment.<\/jats:p>","DOI":"10.1093\/biolre\/ioad090","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T13:50:18Z","timestamp":1691502618000},"page":"772-784","source":"Crossref","is-referenced-by-count":7,"title":["Smoothened mediates medaka spermatogonia proliferation via Gli1\u2013Rgcc\u2013Cdk1 axis"],"prefix":"10.1093","volume":"109","author":[{"given":"Changle","family":"Zhao","sequence":"first","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"},{"name":"Southwest University , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"},{"name":"Southwest University , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City , Key Laboratory of Freshwater 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"},{"name":"Southwest University , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Tao","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"},{"name":"Southwest University , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deshou","family":"Wang","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , China"},{"name":"Southwest University , Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Laboratory of Aquatic Science of Chongqing, School of Life Sciences, , Chongqing , 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