Cug2 is essential for normal mitotic control and CNS development in zebrafish

BMC Dev Biol. 2011 Aug 15:11:49. doi: 10.1186/1471-213X-11-49.

Abstract

Background: We recently identified a novel oncogene, Cancer-upregulated gene 2 (CUG2), which is essential for kinetochore formation and promotes tumorigenesis in mammalian cells. However, the in vivo function of CUG2 has not been studied in animal models.

Results: To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS). Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate.

Conclusions: Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism*
  • Chromosome Aberrations / embryology
  • Chromosomes / genetics
  • Gene Expression Regulation, Developmental*
  • Kinetochores / metabolism
  • Mitosis / physiology*
  • Morpholinos / genetics
  • Neurodegenerative Diseases / genetics
  • Neurogenesis / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Sequence Alignment
  • Spindle Apparatus / genetics
  • Spindle Apparatus / pathology
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Morpholinos
  • Nuclear Proteins
  • RNA, Small Interfering
  • Zebrafish Proteins
  • cenpw protein, zebrafish