Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development

Development. 2011 Jul;138(13):2661-72. doi: 10.1242/dev.066381. Epub 2011 May 25.

Abstract

Mitosis is controlled by multiple kinases that drive cell cycle progression and prevent chromosome mis-segregation. Aurora kinase B interacts with survivin, borealin and incenp to form the chromosomal passenger complex (CPC), which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis. Whereas genetic ablation of survivin, borealin or incenp results in early lethality at the morula stage, we show here that aurora B is dispensable for CPC function during early cell divisions and aurora B-null embryos are normally implanted. This is due to a crucial function of aurora C during these early embryonic cycles. Expression of aurora C decreases during late blastocyst stages resulting in post-implantation defects in aurora B-null embryos. These defects correlate with abundant prometaphase figures and apoptotic cell death of the aurora B-deficient inner cell mass. Conditional deletion of aurora B in somatic cells that do not express aurora C results in chromosomal misalignment and lack of chromosome segregation. Re-expression of wild-type, but not kinase-dead, aurora C rescues this defect, suggesting functional overlap between these two kinases. Finally, aurora B-null cells partially arrest in the presence of nocodazole, suggesting that this kinase is not essential for the spindle assembly checkpoint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • Blastocyst / metabolism
  • Cell Division / genetics
  • Cell Division / physiology
  • Cells, Cultured
  • Chromosome Segregation / genetics
  • Chromosome Segregation / physiology
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Mice
  • Mice, Transgenic
  • Mitosis / genetics
  • Mitosis / physiology
  • Pregnancy
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Zygote / metabolism

Substances

  • Aurkb protein, mouse
  • Aurkc protein, mouse
  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases