PMID- 34124073
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240402
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 9
DP  - 2021
TI  - Echinoderm Microtubule Associated Protein Like 1 Is Indispensable for Oocyte 
      Spindle Assembly and Meiotic Progression in Mice.
PG  - 687522
LID - 10.3389/fcell.2021.687522 [doi]
LID - 687522
AB  - Completion of the first meiosis is an essential prerequisite for producing a 
      functionally normal egg for fertilization and embryogenesis, but the precise 
      mechanisms governing oocyte meiotic progression remains largely unclear. Here, we 
      report that echinoderm microtubule associated protein (EMAP) like 1 (EML1), a 
      member of the conserved EMAP family proteins, plays a crucial role in the control 
      of oocyte meiotic progression in the mouse. Female mice carrying an ENU-induced 
      nonsense mutation (c.1956T > A; p.Tyr652( *)) of Eml1 are infertile, and the 
      majority of their ovulated oocytes contain abnormal spindles and misaligned 
      chromosomes. In accordance with the mutant oocyte phenotype, we find that EML1 is 
      colocalized with spindle microtubules during the process of normal oocyte meiotic 
      maturation, and knockdown (KD) of EML1 by specific morpholinos in the fully grown 
      oocytes (FGOs) disrupts the integrity of spindles, and delays meiotic 
      progression. Moreover, EML1-KD oocytes fail to progress to metaphase II (MII) 
      stage after extrusion of the first polar body, but enter into interphase and form 
      a pronucleus containing decondensed chromatins. Further analysis shows that 
      EML1-KD impairs the recruitment of gamma-tubulin and pericentrin to the spindle 
      poles, as well as the attachment of kinetochores to microtubules and the proper 
      inactivation of spindle assembly checkpoint at metaphase I (MI). The loss of EML1 
      also compromises the activation of maturation promoting factor around the time of 
      oocyte resumption and completion of the first meiosis, which, when corrected by 
      WEE1/2 inhibitor PD166285, efficiently rescues the phenotype of oocyte delay of 
      meiotic resumption and inability of reaching MII. Through IP- mass spectrometry 
      analysis, we identified that EML1 interacts with nuclear distribution gene C 
      (NUDC), a critical mitotic regulator in somatic cells, and EML1-KD disrupts the 
      specific localization of NUDC at oocyte spindles. Taken together, these data 
      suggest that EML1 regulates acentrosomal spindle formation and the progression of 
      meiosis to MII in mammalian oocytes, which is likely mediated by distinct 
      mechanisms.
CI  - Copyright (c) 2021 Yin, Zhang, Wang, Hu, Hou, Fang, Yin, Li, Shi and Su.
FAU - Yin, Hong
AU  - Yin H
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
FAU - Zhang, Teng
AU  - Zhang T
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
FAU - Wang, Hao
AU  - Wang H
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
FAU - Hu, Xin
AU  - Hu X
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
FAU - Hou, Xuan
AU  - Hou X
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
FAU - Fang, Xianbao
AU  - Fang X
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
FAU - Yin, Yaoxue
AU  - Yin Y
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
FAU - Li, Hui
AU  - Li H
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Sciences, Shandong University, Qingdao, China.
FAU - Shi, Lanying
AU  - Shi L
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Sciences, Shandong University, Qingdao, China.
FAU - Su, You-Qiang
AU  - Su YQ
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, China.
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Sciences, Shandong University, Qingdao, China.
AD  - Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child 
      Health Hospital, Nanjing Medical University, Nanjing, China.
AD  - Collaborative Innovation Center of Genetics and Development, Fudan University, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20210528
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8194061
OTO - NOTNLM
OT  - CDK1
OT  - EML1
OT  - female fertility
OT  - meiosis
OT  - oocyte
OT  - spindle
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/15 06:00
MHDA- 2021/06/15 06:01
PMCR- 2021/01/01
CRDT- 2021/06/14 09:50
PHST- 2021/03/29 00:00 [received]
PHST- 2021/05/04 00:00 [accepted]
PHST- 2021/06/14 09:50 [entrez]
PHST- 2021/06/15 06:00 [pubmed]
PHST- 2021/06/15 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2021.687522 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 May 28;9:687522. doi: 10.3389/fcell.2021.687522. 
      eCollection 2021.