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CKS1 Germ Line Exclusion Is Essential for the Transition from Meiosis to Early Embryonic Development

Zdenka Ellederova1,2, Sonia Del Rincon1,3, Marketa Koncicka4,5

  • 1Tumor Initiation and Maintenance Program, Sanford | Burnham | Prebys Medical Discovery Institute, La Jolla, California, USA.

Molecular and Cellular Biology
|April 17, 2019
PubMed

Insights

Cell division cycle kinase subunit 2 (CKS2) is essential for regulating maturation-promoting factor (MPF) activity during meiosis. Its absence causes developmental defects, highlighting the importance of CKS2 in germ cells.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • Cell division cycle (Cdc) kinase subunit (CKS) proteins regulate cyclin-dependent kinases (CDKs).
  • Mammals have two CKS paralogs, CKS1 and CKS2, with CKS2 uniquely expressed in the germ line.
  • The precise molecular roles of CKS proteins in cell division and development require further elucidation.

Purpose of the Study:

  • To investigate the role of CKS2 in regulating CDK activity during meiosis.
  • To determine the impact of CKS2 deficiency on meiotic progression and embryonic development.
  • To assess the potential compensatory role of CKS1 in meiosis.

Main Methods:

  • Generation and analysis of cks2 knockout mice.
  • Assessment of meiotic progression, MPF activity, and germ cell development in cks2 oocytes.
  • Microinjection of MPF and CKS2 into cks2 oocytes.
  • Generation and analysis of cks2 knock-in mice.

Main Results:

  • cks2 oocytes exhibit reduced and delayed MPF activity, leading to defects in germinal vesicle breakdown (GVBD), APC/C activation, and meiotic spindle assembly.
  • CKS2 deficiency results in significantly reduced levels of CDK1 and cyclins A1/B1 in germ cells.
  • CKS1 can compensate for CKS2 in meiosis in vivo, but homozygous cks2 embryos show developmental arrest.
  • CKS2-dependent MPF function is critical for GVBD.

Conclusions:

  • CKS2 is a crucial regulator of MPF functions essential for successful meiosis.
  • The absence of CKS2 leads to severe meiotic and developmental defects.
  • Exclusion of CKS1 from the germ line is necessary for proper embryonic development, indicating a specialized role for CKS2 in reproduction.
Keywords:
CKScyclin-dependent kinasesdevelopmental biologymeiosis

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