title: Oocyte-specific deletion of N-WASP does not affect oocyte polarity, but causes failure of meiosis II completion.
abstract: There is an unexplored physiological role of N-WASP (neural Wiskott-Aldrich syndrome protein) in oocyte maturation that prevents completion of second meiosis.
  
  
  
  In mice, N-WASP deletion did not affect oocyte polarity and asymmetric meiotic division in first meiosis, but did impair midbody formation and second meiosis completion.
  
  
  
  N-WASP regulates actin dynamics and participates in various cell activities through the RHO-GTPase-Arp2/3 (actin-related protein 2/3 complex) pathway, and specifically the Cdc42 (cell division cycle 42)-N-WASP-Arp2/3 pathway. Differences in the functions of Cdc42 have been obtained from in vitro compared to in vivo studies.
  
  
  
  By conditional knockout of N-WASP in mouse oocytes, we analyzed its in vivo functions by employing a variety of different methods including oocyte culture, immunofluorescent staining and live oocyte imaging. Each experiment was repeated at least three times, and data were analyzed by paired-samples t-test.
  
  
  
  Oocyte-specific deletion of N-WASP did not affect the process of oocyte maturation including spindle formation, spindle migration, polarity establishment and maintenance, and homologous chromosome or sister chromatid segregation, but caused failure of cytokinesis completion during second meiosis (P < 0.001 compared to control). Further analysis showed that a defective midbody may be responsible for the failure of cytokinesis completion.
  
  
  
  The present study did not include a detailed analysis of the mechanisms underlying the results, which will require more extensive further investigations.
  
  
  
  N-WASP may play an important role in mediating and co-ordinating the activity of the spindle (midbody) and actin (contractile ring constriction) when cell division occurs. The findings are important for understanding the regulation of oocyte meiosis completion and failures in this process that affect oocyte quality.
  
  
  
  None.
  
  
  
  This work was supported by the National Basic Research Program of China (No. 2012CB944404) and the National Natural Science Foundation of China (Nos 30930065, 31371451, 31272260 and 31530049). There are no potential conflicts of interests.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China University of Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Xue-Shan
authors.initials: XS
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Meng-Wen
authors.initials: MW
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Zong-Zhe
authors.initials: ZZ
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China University of Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Tie-Gang
authors.initials: TG
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Ming-Zhe
authors.initials: MZ
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China University of Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Ouyang
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China University of Chinese Academy of Sciences, Beijing 100101, P.R. China sunqy@ioz.ac.cn.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology; D005260:Female; D008297:Male; D008540:Meiosis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000172:deficiency* / Q000235:genetics*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D020764:cdc42 GTP-Binding Protein
keywords: N-WASP; cytokinesis; meiosis II; oocyte; polarity