1. WDR62 is required for centriole duplication in spermatogenesis and manchette removal in spermiogenesis.
- Author
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Ho UY, Feng CA, Yeap YY, Bain AL, Wei Z, Shohayeb B, Reichelt ME, Homer H, Khanna KK, Bowles J, and Ng DCH
- Subjects
- Animals, Cell Cycle genetics, Cell Cycle Proteins genetics, Centrioles metabolism, Cytoskeleton metabolism, Female, Male, Meiosis, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins genetics, Spermatids metabolism, Spermatogenesis physiology, Spermatozoa metabolism, Testis metabolism, Cell Cycle Proteins metabolism, Centrioles genetics, Nerve Tissue Proteins metabolism, Spermatogenesis genetics
- Abstract
WDR62 is a scaffold protein involved in centriole duplication and spindle assembly during mitosis. Mutations in WDR62 can cause primary microcephaly and premature ovarian insufficiency. We have generated a genetrap mouse model deficient in WDR62 and characterised the developmental effects of WDR62 deficiency during meiosis in the testis. We have found that WDR62 deficiency leads to centriole underduplication in the spermatocytes due to reduced or delayed CEP63 accumulation in the pericentriolar matrix. This resulted in prolonged metaphase that led to apoptosis. Round spermatids that inherited a pair of centrioles progressed through spermiogenesis, however, manchette removal was delayed in WDR62 deficient spermatids due to delayed Katanin p80 accumulation in the manchette, thus producing misshapen spermatid heads with elongated manchettes. In mice, WDR62 deficiency resembles oligoasthenoteratospermia, a common form of subfertility in men that is characterised by low sperm counts, poor motility and abnormal morphology. Therefore, proper WDR62 function is necessary for timely spermatogenesis and spermiogenesis during male reproduction.
- Published
- 2021
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