Citron kinase is required for postnatal neurogenesis in the hippocampus

Dev Neurosci. 2007;29(1-2):113-23. doi: 10.1159/000096216.

Abstract

The dentate gyrus is a site of continual neurogenesis in the postnatal mammalian brain. Here we investigated postnatal neurogenesis in the citron kinase (citron-K) null-mutant rat (flathead). The flathead rat has substantial deficits in embryonic neurogenesis that are due to failed cytokinesis and cell death. We report here the loss of citron-K function has an even severer effect on postnatal neurogenesis in the dentate gyrus. Analysis of phosphorylated histone H3 expression in postnatal neurogenic regions of the flathead mutant revealed a complete lack of mitotic cells in the dentate gyrus and a large reduction in the number of dividing cells in the flathead subventricular zone. Examination of 5-bromodeoxyuridine incorporation in the flathead rat revealed that the flathead rat had a 99% reduction in the number of newly generated cells in the dentate gyrus at postnatal day 10. In addition, doublecortin-positive cells were essentially absent from the postnatal flathead dentate gyrus which also lacked the vimentin- and nestin-positive radial glia scaffold that defines the neurogenic niche in the postnatal subgranular zone. Together these results indicate that postnatal neurogenesis in the dentate gyrus is eliminated by loss of citron-K function, and suggests that a citron-K-dependent progenitor lineage forms the postnatal neuronal progenitor population in the dentate gyrus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Count
  • Cell Cycle Proteins / genetics*
  • Cell Differentiation / genetics*
  • Cell Proliferation*
  • Dentate Gyrus / abnormalities*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental / genetics
  • Histones / genetics
  • Histones / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Mitosis / genetics
  • Nervous System Malformations / genetics*
  • Nervous System Malformations / metabolism
  • Nervous System Malformations / physiopathology
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein-Serine-Threonine Kinases / genetics*
  • Rats
  • Rats, Mutant Strains
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • Cell Cycle Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • citron-kinase
  • Protein-Serine-Threonine Kinases