Editors' ChoiceNeuroscience

Wnt Signals in the Mature Hippocampus

Science's STKE  01 Nov 2005:
Vol. 2005, Issue 308, pp. tw385
DOI: 10.1126/stke.3082005tw385

New dentate granule neurons derived from adult hippocampal stem (or progenitor) cells (AHPs) in the subgranular zone (SGZ) of the dentate gyrus (one of two regions in the adult mammalian brain where generation of new neurons from neural stem cells occurs) may play a role in hippocampal plasticity and learning. Although signals from neighboring astrocytes are known to regulate AHP proliferation and differentiation, the precise nature of these signals has been unclear. Lie et al. combined in situ hybridization with reverse transcription polymerase chain reaction analysis to show that Wnt3 was expressed in astrocytes near the SGZ of adult mice and that the Wnt receptor Frizzled 1 and components of the Wnt/β-catenin pathway (Dishevelled1 and Axin) were expressed in AHPs. Moreover, analysis of mice expressing a Wnt/β-catenin reporter indicated that this pathway was active in the SGZ and dentate granule cell layer. Coculture of AHPs with hippocampal astrocytes stimulated Wnt/β-catenin signaling in cells that developed neuronal markers, whereas differentiation into neurons of AHPs cocultured with hippocampal astrocytes was decreased in the presence of a Wnt inhibitor or when a dominant-negative inhibitor of Wnt/β-catenin signaling was expressed. Wnt3 overexpression in cultured AHPs enhanced neurogenesis by stimulating neuroblast proliferation and promoting neuronal fate commitment. Neurogenesis in the dentate gyrus of adult rats was reduced when Wnt signaling was inhibited by expression of a secreted Wnt1 mutant, whereas Wnt3 overexpression promoted adult hippocampal neurogenesis. Thus, Wnt signaling, which plays a critical role during brain development, also appears to regulate neurogenesis in the adult hippocampus.

D.-C. Lie, S. A. Colamarino, H.-J. Song, L. Désiré, H. Mira, A. Consiglio, E. S. Lein, S. Jessberger, H. Lansford, A. R. Dearie, F. H. Gage, Wnt signalling regulates adult hippocampal neurogenesis. Nature 437, 1370-1375 (2005). [PubMed]