Germ cells form the basis for sexual reproduction by producing gametes. In ovaries, primordial germ cells exit the cell cycle and the pluripotency-associated state, differentiate into oogonia, and initiate meiosis. Despite the importance of germ cell differentiation for sexual reproduction, signaling pathways regulating their fate remain largely unknown. Here, we show in mouse embryonic ovaries that germ cell–intrinsic β-catenin activity maintains pluripotency and that its repression is essential to allow differentiation and meiosis entry in a timely manner. Accordingly, in β-catenin loss-of-function and gain-of-function mouse models, the germ cells precociously enter meiosis or remain in the pluripotent state, respectively. We further show that interaction of β-catenin and the pluripotent-associated factor POU5F1 in the nucleus is associated with germ cell pluripotency. The exit of this complex from the nucleus correlates with germ cell differentiation, a process promoted by the up-regulation of Znrf3, a negative regulator of WNT/β-catenin signaling. Together, these data identify the molecular basis of the transition from primordial germ cells to oogonia and demonstrate that β-catenin is a central gatekeeper in ovarian differentiation and gametogenesis.

生殖细胞通过产生配子形成有性生殖的基础。在卵巢中，原始生殖细胞退出细胞周期和多能性相关状态，分化为卵原细胞，并启动减数分裂。尽管生殖细胞分化对于有性生殖很重要，但调节其命运的信号通路仍然很大程度上未知。在这里，我们在小鼠胚胎卵巢中证明，生殖细胞固有的β-连环蛋白活性可维持多能性，并且其抑制对于及时分化和进入减数分裂至关重要。因此，在β-连环蛋白功能丧失和功能获得的小鼠模型中，生殖细胞分别提前进入减数分裂或保持多能状态。我们进一步表明，β-连环蛋白和细胞核中多能相关因子 POU5F1 的相互作用与生殖细胞多能性相关。该复合物从细胞核中退出与生殖细胞分化相关，生殖细胞分化是由Znrf3 （WNT/β-连环蛋白信号传导的负调节因子）上调促进的过程。这些数据共同确定了从原始生殖细胞向卵原细胞转变的分子基础，并证明 β-连环蛋白是卵巢分化和配子发生的中心看门人。