Proliferation of hippocampal progenitors relies on p27-dependent regulation of Cdk6 kinase activity

Nicolas Caron, Emmanuelle C. Genin, Quentin Marlier, Sébastien Verteneuil, Pierre Beukelaers, Laurence Morel, Miaofen G. Hu, Philip W. Hinds, Laurent Nguyen, Renaud Vandenbosch, Brigitte Malgrange

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Neural stem cells give rise to granule dentate neurons throughout life in the hippocampus. Upon activation, these stem cells generate fast proliferating progenitors that complete several rounds of divisions before differentiating into neurons. Although the mechanisms regulating the activation of stem cells have been intensively studied, little attention has been given so far to the intrinsic machinery allowing the expansion of the progenitor pool. The cell cycle protein Cdk6 positively regulates the proliferation of hippocampal progenitors, but the mechanism involved remains elusive. Whereas Cdk6 functions primarily as a cell cycle kinase, it can also act as transcriptional regulator in cancer cells and hematopoietic stem cells. Using mouse genetics, we show here that the function of Cdk6 in hippocampal neurogenesis relies specifically on its kinase activity. The present study also reveals a specific regulatory mechanism for Cdk6 in hippocampal progenitors. In contrast to the classical model of the cell cycle, we observe that the Cip/Kip family member p27, rather than the Ink4 family, negatively regulates Cdk6 in the adult hippocampus. Altogether, our data uncover a unique, cell type-specific regulatory mechanism controlling the expansion of hippocampal progenitors, where Cdk6 kinase activity is modulated by p27.

Original languageEnglish (US)
Pages (from-to)3817-3827
Number of pages11
JournalCellular and Molecular Life Sciences
Volume75
Issue number20
DOIs
StatePublished - Oct 1 2018
Externally publishedYes

Keywords

  • Adult neurogenesis
  • Cdk inhibitors
  • Cdks
  • Cell cycle
  • Dentate gyrus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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