Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)-cyclinD1 complex in the adult mouse hippocampus cell-autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4-cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells.

Details

Original languageEnglish
Pages (from-to)937-948
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number5
Publication statusPublished - 9 May 2011
Peer-reviewedYes

External IDs

Scopus 79956125698
PubMed 21482697
PubMedCentral PMC3092341
ORCID /0000-0002-0320-4223/work/151983044

Keywords

Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

Keywords

  • Animals, Cyclin D1/biosynthesis, Cyclin-Dependent Kinase 4/biosynthesis, Gene Expression Regulation/physiology, HeLa Cells, Hippocampus/cytology, Humans, Mice, Neural Stem Cells/metabolism, Neurogenesis/physiology

Library keywords