title: JNK signaling regulates E-cadherin junctions in germline cysts and determines primordial follicle formation in mice.
abstract: Physiologically, the size of the primordial follicle pool determines the reproductive lifespan of female mammals, while its establishment largely depends on a process of germline cyst breakdown during the perinatal period. 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 increased as germline cyst breakdown progressed. Importantly, disruption of JNK signaling with a specific inhibitor (SP600125) or knockdown 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, inhibition of JNK signaling leads to aberrantly enhanced localization of E-cadherin at oocyte-oocyte contact sites. WNT4 expression is upregulated after SP600125 treatment. Additionally, similar to the effect of 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.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Wanbao
authors.initials: W
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhengpin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Xin
authors.affiliation: National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing 102206, China.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Lizhao
authors.initials: L
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China glxiachina@sohu.com.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xia
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D005854:Germ Cells / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D038081:Organogenesis; D006080:Ovarian Follicle / Q000378:metabolism*; D059748:Proteolysis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D060528:Wnt4 Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D060528:Wnt4 Protein; D051736:Proto-Oncogene Proteins c-mdm2; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Cadherin 1; E-cadherin; Germline cyst; JNK; MAPK; Primordial follicle; WNT4