Loss of Borealin/DasraB leads to defective cell proliferation, p53 accumulation and early embryonic lethality

Mech Dev. May-Jun 2008;125(5-6):441-50. doi: 10.1016/j.mod.2008.01.011. Epub 2008 Feb 5.

Abstract

Borealin/DasraB is a member of the chromosomal passenger protein complex (CPC) required for proper segregation of chromosomes during mitosis. In Drosophila melanogaster, inactivation of Borealin/DasraB results in polyploidy, delayed mitosis and abnormal tissue development, indicating its critical role for cell proliferation. However, the in vivo role of mammalian Borealin/DasraB remains unclear. Here, we analyzed the expression of Borealin/DasraB and found that borealin is widely expressed in embryonic tissues and later restricted to adult tissues which relies on rapid cell proliferation. To determine the role of borealin during mouse development, we generated borealin-null mice through targeted disruption. While heterozygous mice developed normally, disruption of both borealin alleles resulted in early embryonic lethality by 5.5 dpc (days postcoitus) due to mitotic defects and apoptosis in blastocyst cells that showed microtubule disorganization and no CPC enrichment. At 5.5 dpc, borealin-null embryos exhibited excessive apoptosis and elevated expression of p53. However, loss of p53 did not abrogate or delay embryonic lethality, revealing that Borealin/DasraB inactivation triggered impaired mitosis and apoptosis though p53-independent mechanisms. Our data show that Borealin/DasraB is essential for cell proliferation during early embryonic development, and its early embryonic lethality cannot be rescued by the loss of p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blastocyst / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Chromosomal Proteins, Non-Histone
  • Developmental Biology / methods
  • Gene Expression Regulation, Developmental*
  • Genes, p53
  • Heterozygote
  • Mice
  • Mice, Transgenic
  • Microtubules / metabolism
  • Mitosis
  • Models, Genetic
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / physiology*
  • Ploidies
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • CDCA8 protein, mouse
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Nuclear Pore Complex Proteins
  • Tumor Suppressor Protein p53