Cdk5 is essential for adult hippocampal neurogenesis

Diane C. Lagace, David R. Benavides, Janice W. Kansy, Marina Mapelli, Paul Greengard, James A. Bibb, Amelia J. Eisch

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The molecular factors regulating adult neurogenesis must be understood to harness the therapeutic potential of neuronal stem cells. Although cyclin-dependent kinase 5 (Cdk5) plays a critical role in embryonic corticogenesis, its function in adult neurogenesis is unknown. Here, we assessed the role of Cdk5 in the generation of dentate gyrus (DG) granule cell neurons in adult mice. Cre recombinase-mediated conditional knockout (KO) of Cdk5 from stem cells and their progeny in the DG subgranular zone (SGZ) prevented maturation of new neurons. In addition, selective KO of Cdk5 from mature neurons throughout the hippocampus reduced the number of immature neurons. Furthermore, Cdk5 gene deletion specifically from DG granule neurons via viral-mediated gene transfer also resulted in fewer immature neurons. In each case, the total number of proliferating cells was unaffected, indicating that Cdk5 is necessary for progression of adult-generated neurons to maturity. This role for Cdk5 in neurogenesis was activating-cofactor specific, as p35 KO but not p39 KO mice also had fewer immature neurons. Thus, Cdk5 has an essential role in the survival, but not proliferation, of adult-generated hippocampal neurons through both cell-intrinsic and cell-extrinsic mechanisms.

Original languageEnglish
Pages (from-to)18567-18571
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number47
DOIs
Publication statusPublished - Nov 25 2008

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Cyclin-Dependent Kinase 5
Neurogenesis
Neurons
Dentate Gyrus
Stem Cells
Viral Genes
Gene Deletion
Knockout Mice
Hippocampus
Cell Count

Keywords

  • Cyclin-dependent kinase
  • Dentate gyrus granule cell
  • Doublecortin
  • Nestin-CreERT2
  • Viral-mediated gene transfer

ASJC Scopus subject areas

  • General

Cite this

Lagace, D. C., Benavides, D. R., Kansy, J. W., Mapelli, M., Greengard, P., Bibb, J. A., & Eisch, A. J. (2008). Cdk5 is essential for adult hippocampal neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 105(47), 18567-18571. https://doi.org/10.1073/pnas.0810137105

Cdk5 is essential for adult hippocampal neurogenesis. / Lagace, Diane C.; Benavides, David R.; Kansy, Janice W.; Mapelli, Marina; Greengard, Paul; Bibb, James A.; Eisch, Amelia J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 47, 25.11.2008, p. 18567-18571.

Research output: Contribution to journalArticle

Lagace, Diane C. ; Benavides, David R. ; Kansy, Janice W. ; Mapelli, Marina ; Greengard, Paul ; Bibb, James A. ; Eisch, Amelia J. / Cdk5 is essential for adult hippocampal neurogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 47. pp. 18567-18571.
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