Ontogeny of abnormal brain development in Cdk5(-/-) mice

Toshio Ohshima, Edward C. Gilmore, Karl Herrup, Roscoe O. Brady, Ashok Kulkarni

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cyclin-dependent kinase 5 (Cdk5) was originally identified by its homology to other Cdks. Its expression is predominant in the central nervous system where Cdk5 expression and kinase activity are correlated with the extent of differentiation of neuronal cells and corticogenesis in the developing brain. Cdk5 purified from nervous tissue phosphorylates neuronal cytoskeletal proteins including neurofilament proteins and microtubule- associated protein tau in vitro. These findings indicate that Cdk5 may have unique functions in neuronal cells, especially in the regulation of phosphorylation of cytoskeletal molecules. We reported earlier the generation of Cdk5(-/-) mouse line by gene targeting. Cdk5(-/-) mice exhibit a lack of cortical laminar structure in cerebrum and cerebellum with perinatal mortality. In this study, we analyzed embryonic brains at different ages to define the ontogeny of formation of abnormal brain structure in Cdk5(-/-) mouse embryos. Abnormal lamination patterns are apparent at E16.5 in cerebral and cerebellar cortex, although normal neurogenesis is observed in ventricular zone in Cdk5(-/-) mice. At E18.5 the olfactory bulb also lacks the characteristic structure of cortical lamination. Additionally, the thalamus of Cdk5(-/-) embryos is decreased in size by E18.5. The ontogeny of formation of abnormal brain structures in these mice parallels Cdk5 expression pattern indicating the importance of Cdk5 in corticogenesis.

Original languageEnglish
Pages (from-to)271-281
Number of pages11
JournalDevelopmental Brain Dysfunction
Volume10
Issue number5
Publication statusPublished - 1997 Sep 1
Externally publishedYes

Keywords

  • Cerebellum
  • Cerebral cortex
  • Corticogenesis
  • Cyclin-dependent kinase
  • Embryo
  • Gene targeting
  • Olfactory bulb
  • Thalamus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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  • Cite this

    Ohshima, T., Gilmore, E. C., Herrup, K., Brady, R. O., & Kulkarni, A. (1997). Ontogeny of abnormal brain development in Cdk5(-/-) mice. Developmental Brain Dysfunction, 10(5), 271-281.