Wdr62 is involved in meiotic initiation via activating JNK signaling and associated with POI in humans
journal contributionposted on 01.10.2020, 15:05 authored by Yang Zhou, Yan Qin, Yingying Qin, Binyang Xu, Ting Guo, Hanni Ke, Min Chen, Lianjun Zhang, Feng Han, Yaqiong Li, Axel Behrens, Yaqing Wang, Zhiheng Xu, Zi-Jiang Chen, Fei Gao
Meiosis is a germ cell-specific division that is indispensable for the generation of haploid gametes. However, the regulatory mechanisms of meiotic initiation remain elusive. Here, we report that the Wdr62 (WD40-repeat protein 62) is involved in meiotic initiation as a permissive factor rather than an instructive factor. Knock-out of this gene in a mouse model resulted in female meiotic initiation defects. Further studies demonstrated that Wdr62 is required for RA-induced Stra8 expression via the activation of JNK signaling, and the defects in meiotic initiation from Wdr62-deficient female mice could be partially rescued by JNK1 overexpression in germ cells. More importantly, two novel mutations of the WDR62 gene were detected in patients with premature ovarian insufficiency (POI), and these mutations played dominant-negative roles in regulating Stra8 expression. Hence, this study revealed that Wdr62 is involved in female meiotic initiation via activating JNK signaling, which displays a novel mechanism for regulating meiotic initiation, and mutation of WDR62 is one of the potential etiologies of POI in humans.
Adaptor Proteins, Signal TransducingAnimalsAsian Continental Ancestry GroupCell Cycle ProteinsDisease Models, AnimalFemaleGene DeletionGene Expression RegulationGerm CellsHaploidyHumansMAP Kinase Signaling SystemMaleMeiosisMiceMice, KnockoutMicrotubule-Associated ProteinsNerve Tissue ProteinsPrimary Ovarian InsufficiencySequence Analysis, DNAWhole Exome SequencingBehrens FC001039Developmental Biology0604 Genetics