Back to Search
Start Over
Wdr62 is involved in meiotic initiation via activating JNK signaling and associated with POI in humans
- Source :
- PLoS Genetics, Vol 15, Iss 11, p e1008504 (2019), PLoS Genetics
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- 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.
- Subjects :
- Male
Cancer Research
MAP Kinase Signaling System
Cell Cycle Proteins
Nerve Tissue Proteins
Haploidy
Primary Ovarian Insufficiency
QH426-470
Mice
Asian People
Exome Sequencing
Genetics
Animals
Humans
Molecular Biology
Genetics (clinical)
Ecology, Evolution, Behavior and Systematics
Adaptor Proteins, Signal Transducing
Mice, Knockout
Correction
Sequence Analysis, DNA
Disease Models, Animal
Meiosis
Germ Cells
Gene Expression Regulation
Female
Microtubule-Associated Proteins
Gene Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 15
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....b91731ae8613ffe5fd9ccd06e5c81bb7