WDR62 is involved in spindle assembly by interacting with CEP170 in spermatogenesis

Abstract

WDR62 is the second most common genetic alteration associated with microcephaly. Our previous study demonstrates that Wdr62 is required for germ cell meiosis initiation and the majority of male germ cells are lost as the meiotic defect of first wave spermatogenesis. Strikingly, in this study, we found that the initiation of meiosis of following spermatogenesis was not affected and the germ cells were gradually repopulated at later developmental stages. However, most germ cells were arrested at metaphase of meiosis I and no mature sperm were detected in epididymides. Further studies demonstrated that metaphase I arrest of Wdr62-deficient spermatocytes was caused by asymmetrical distribution of the centrosome and aberrant spindle assembly. Mechanistic studies demonstrated that WDR62 interacted with centriole-associated protein CEP170, and deletion of Wdr62 caused downregulation of the CEP170 protein which in turn led to the aberrant spindle assembly. In summary, this study indicates that the meiosis of first wave spermatogenesis and the following spermatogenesis started from spermatogonium is probably regulated by different mechanisms. We also demonstrated a new function of WDR62 in germ cell meiosis by interacting with CEP170.

Biallelic mutations in KATNAL2 cause male infertility due to oligo‐astheno‐teratozoospermia

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Hbxip (Lamtor5) is essential for embryogenesis and regulates embryonic stem cell differentiation through activating mTORC1

“…Hbxip -/- mice were obtained by crossing Hbxip +/- mice. Genotyping was performed as described previously (Qin et al, 2019). DNA was isolated from dissected embryos or the tail tips of 2-week mice, and then analyzed by PCR.…”

PRMT5 Is Involved in Spermatogonial Stem Cells Maintenance by Regulating Plzf Expression via Modulation of Lysine Histone Modifications

“…IHC and IF procedures were performed as described previously ( Chen et al, 2019 ; Qin et al, 2019 ). Antibodies were diluted as follows: MVH (1:500, Abcam, ab13840), PLZF (1:100, R&D, AF2944), PRMT5 (1:200, Millipore, 07-405), SOX9 (1:500, Millipore, AB5535), STRA8 (1:200, Abcam, ab49405), SYCP3 (1:200, Abcam, ab15093), Ki67 (1:400, Abcam, ab15580), and PH3 (1:400, Millipore, 2605439).…”