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Mol Brain. 2009 Jun 8;2:16. doi: 10.1186/1756-6606-2-16.

Molecular genetic analysis of FGFR1 signalling reveals distinct roles of MAPK and PLCgamma1 activation for self-renewal of adult neural stem cells.

Author information

1
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. dma2@jhmi.edu

Abstract

BACKGROUND:

Neural stem cells (NSCs) are present in the adult mammalian brain and sustain life-long adult neurogenesis in the dentate gyrus of the hippocampus. In culture, fibroblast growth factor-2 (FGF-2) is sufficient to maintain the self-renewal of adult NSCs derived from the adult rat hippocampus. The underlying signalling mechanism is not fully understood.

RESULTS:

In the established adult rat NSC culture, FGF-2 promotes self-renewal by increasing proliferation and inhibiting spontaneous differentiation of adult NSCs, accompanied with activation of MAPK and PLC pathways. Using a molecular genetic approach, we demonstrate that activation of FGF receptor 1 (FGFR1), largely through two key cytoplasmic amino acid residues that are linked to MAPK and PLC activation, suffices to promote adult NSC self-renewal. The canonical MAPK, Erk1/2 activation, is both required and sufficient for the NSC expansion and anti-differentiation effects of FGF-2. In contrast, PLC activation is integral to the maintenance of adult NSC characteristics, including the full capacity for neuronal and oligodendroglial differentiation.

CONCLUSION:

These studies reveal two amino acid residues in FGFR1 with linked downstream intracellular signal transduction pathways that are essential for maintaining adult NSC self-renewal. The findings provide novel insights into the molecular mechanism regulating adult NSC self-renewal, and pose implications for using these cells in potential therapeutic applications.

PMID:
19505325
PMCID:
PMC2700800
DOI:
10.1186/1756-6606-2-16
[Indexed for MEDLINE]
Free PMC Article
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