Related Experiment Video

Updated: Jun 25, 2026

Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
11:13

Using Mouse Oocytes to Assess Human Gene Function During Meiosis I

Published on: April 10, 2018

MIS12 Is Required for Kinetochore-Microtubule Attachment in Oocyte Meiosis

Jian Li1, Chun-Hui Zhang1, Yong Wang1

  • 1Department of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 24, 2026
PubMed

Insights

MIS12 is essential for accurate chromosome segregation in oocyte meiosis by ensuring kinetochore-microtubule attachment. This study reveals MIS12 directly binds microtubules, a novel mechanism critical for spindle assembly checkpoint signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Reproductive Biology

Background:

  • Accurate kinetochore-microtubule (K-MT) attachment is vital for chromosome segregation during oocyte meiosis.
  • The NDC80 complex, part of the KNL1-MIS12-NDC80 (KMN) network, is traditionally linked to K-MT attachment.

Purpose of the Study:

  • To investigate the role of MIS12 in kinetochore-microtubule attachment in mammalian oocytes.
  • To elucidate the molecular mechanism of MIS12 in K-MT interaction and spindle assembly checkpoint (SAC) signaling.

Main Methods:

  • Utilized a conditional knockout (cKO) mouse model to deplete MIS12.
  • Performed protein localization analysis and chromosome spreading assays.
  • Investigated MIS12 interaction with β-tubulin and its effect on KNL1 assembly.

Main Results:

  • Endogenous MIS12 localizes to kinetochores in both mouse and human oocytes.
  • MIS12 depletion severely disrupts K-MT attachment in both meiotic divisions, independent of NDC80.
  • MIS12 directly interacts with β-tubulin (TUBB3, TUBB5), essential for microtubule attachment.
  • MIS12 is required for SAC signaling by stabilizing KNL1 assembly.

Conclusions:

  • Establishes the canonical and essential role of kinetochore-localized MIS12 in oocyte meiosis.
  • Redefines MIS12's function through direct microtubule binding, offering a new paradigm for KMN network-mediated K-MT attachment.
Keywords:
K‐MT attachmentMIS12MeiosisOocyteTUBB3

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