FGF signaling is necessary for neurogenesis in young mice and sufficient to reverse its decline in old mice

Wenfei Kang, Jean M. Hébert

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The mechanisms regulating hippocampal neurogenesis remain poorly understood. Particularly unclear is the extent to which age-related declines in hippocampal neurogenesis are due to an innate decrease in precursor cell performance or to changes in the environment of these cells. Several extracellular signaling factors that regulate hippocampal neurogenesis have been identified. However, the role of one important family, FGFs, remains uncertain. Although a body of literature suggests that FGFs can promote the proliferation of cultured adult hippocampal precursor cells, their requirement for adult hippocampal neurogenesis in vivo and the cell types within the neurogenic lineage that might depend on FGFs remain unclear. Here, specifically targeting adult neural precursor cells, we conditionally express an activated form of an FGF receptor or delete the FGF receptors that are expressed in these cells.Wefind that FGF receptors are required for neural stem-cell maintenance and that an activated receptor expressed in all precursors can increase the number of neurons produced. Moreover, in older mice, an activated FGF receptor can rescue the age-related decline in neurogenesis to a level found in young adults. These results suggest that the decrease in neurogenesis with age is not simply due to fewer stem cells, but also to declining signals in their niche. Thus, enhancing FGF signaling in precursors can be used to reverse age-related declines in hippocampal neurogenesis.

Original languageEnglish (US)
Pages (from-to)10217-10223
Number of pages7
JournalJournal of Neuroscience
Volume35
Issue number28
DOIs
StatePublished - Jul 15 2015

Keywords

  • Aging
  • Dentate gyrus
  • FGF receptor
  • Hippocampus
  • Mouse
  • Neurogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

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