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However, the mechanisms regulating this process are poorly understood. Here we demonstrate that c-Jun amino-terminal kinase (JNK) signaling is crucial for germline cyst breakdown and primordial follicle formation. JNK was specifically localized in oocytes and its activity was increased as germline cyst breakdown progressed. Importantly, the disruption of JNK signaling with its specific inhibitor (SP600125) or knock-down technology (Lenti-JNK-shRNAs) resulted in significantly suppressed cyst breakdown and primordial follicle formation in cultured mouse ovaries. Our results show that E-cadherin is intensely expressed in germline cysts, and that its decline is necessary for oocyte release from the cyst. However, the inhibition of JNK signaling leads to aberrantly enhanced localization of E-cadherin at oocyte\u2013oocyte contact sites. Meanwhile, WNT4 expression is upregulated after SP600125 treatment. Additionally, similar to SP600125 treatment, WNT4 overexpression delays cyst breakdown; and is accompanied by abnormal E-cadherin expression patterns. In conclusion, our results suggest that JNK signaling, which is inversely correlated with WNT4, plays an important role in perinatal germline cyst breakdown and primordial follicle formation by regulating E-cadherin junctions between oocytes in mouse ovaries.<\/jats:p>","DOI":"10.1242\/dev.132175","type":"journal-article","created":{"date-parts":[[2016,3,25]],"date-time":"2016-03-25T02:16:53Z","timestamp":1458872213000},"source":"Crossref","is-referenced-by-count":25,"title":["JNK signaling regulates E-cadherin junctions in germline cysts and determines primordial follicle formation in mice"],"prefix":"10.1242","author":[{"given":"Wanbao","family":"Niu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengpin","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiliang","family":"Xin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijing","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhao","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Wen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoliang","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042608340878300_DEV132175C1","doi-asserted-by":"publisher","first-page":"25431","DOI":"10.1074\/jbc.M113.527267","article-title":"Inhibition of epithelial to mesenchymal transition by E-cadherin up-regulation via repression of slug transcription and inhibition of E-cadherin degradation: dual role of scaffold\/matrix attachment region-binding protein 1 (SMAR1) in breast cancer cells","volume":"289","author":"Adhikary","year":"2014","journal-title":"J. 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