JNK signaling regulates E-cadherin junctions in germline cysts and determines primordial follicle formation in mice
JNK signaling regulates E-cadherin junctions in germline cysts and determines primordial follicle formation in mice
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JNK 信号调节种系囊肿中的 E-钙粘蛋白连接并决定小鼠原始卵泡的形成
DOI：
10.1242/dev.132175
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发表时间：
2016-05-15
期刊：
影响因子：
4.6
通讯作者：
Xia, Guoliang
中科院分区：
文献类型：
--
作者：
Niu, Wanbao;Wang, Ye;Xia, Guoliang
在生理上，原始卵泡池的大小决定了雌性哺乳动物的生殖寿命，而其建立在很大程度上取决于围产期种系囊肿破裂的过程。调控这一过程的机制尚不清楚。本研究表明，c-Jun氨基末端激酶（JNK）信号在种系囊肿破裂和原始卵泡形成中起着至关重要的作用。JNK特异性定位于卵母细胞，其活性随着种系囊肿破裂的进展而增加。重要的是，使用特定抑制剂（SP600125）或敲低技术（lentii -JNK- shrnas）破坏JNK信号可显著抑制培养小鼠卵巢中的囊肿破裂和原始卵泡形成。我们的研究结果表明，E-cadherin在种系囊肿中强烈表达，其下降是卵母细胞从囊肿中释放的必要条件。然而，JNK信号的抑制导致e-钙粘蛋白在卵母细胞-卵母细胞接触部位的定位异常增强。SP600125处理后WNT4表达上调。此外，与SP600125治疗效果相似，WNT4过表达延迟囊肿破裂，并伴有E-cadherin异常表达模式。综上所述，我们的研究结果表明，JNK信号与WNT4呈负相关，通过调节小鼠卵巢内卵母细胞之间的E-cadherin连接，在围产期种系囊肿破裂和原始卵泡形成中发挥重要作用。摘要：在小鼠实验中，JNK和WNT4在种系囊肿破裂和原始卵泡形成过程中拮抗调节E-cadherin表达和卵母细胞-卵母细胞粘附。
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. Summary: In mice, JNK and WNT4 antagonistically regulate E-cadherin expression and oocyte-oocyte adhesion during germline cyst breakdown and primordial follicle formation.