Stn1 promotes zebrafish oocyte development via amplifying Wnt/β-catenin signaling

Wnt/β-catenin signaling regulates oocyte development in vertebrates. However, the dynamics of Wnt/β-catenin signaling in oocyte progression remain unclear. Here, we analyze oocytes across different developmental stages in zebrafish and find that the activity of Wnt/β-catenin signaling sharply increases when oocytes reach a size of 10 to 45 μm (stage IA to middle stage IB) and subsequently declines rapidly. In addition, we show that expression of the CST complex subunit Stn1 is enriched in germ cells. Stn1 interacts with the transcription factor Tcf/Lef, facilitates its association with promoters of germ cell-specific genes, thereby enhancing Wnt/β-catenin signaling activity in oocytes. Genetic deletion of stn1 leads to massive loss of oocytes prior to or during their development to stage IB, resulting in a male-like phenotype associated with infertility. Temporal activation of the Wnt/β-catenin signaling pathway partially restores germ cell loss and facilitates oocyte development to stage IB. Our findings highlight the importance of Wnt/β-catenin signaling in promoting the expression of germ cell-specific genes and provide novel insights into the physiological function of Stn1 in maintaining oocyte development in zebrafish.