1. Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA
2. GSF-National Research Centre for Environment and Health, Institute of Developmental Genetics, 85764 Munich, Neuherberg, Germany
3. Institute for Cell Engineering, Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
4. *These authors contributed equally to this work

Correspondence to: Dieter-Chichung Lie^1,2,4Fred H. Gage¹ Correspondence and requests for materials should be addressed to F.H.G. (Email: gage@salk.edu) or D.C.L. (Email: chichung.lie@gsf.de).

Abstract

The generation of new neurons from neural stem cells is restricted to two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyrus¹. In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population¹. The identity of these signals is largely unknown. Here we show that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development². We also show that the Wnt/-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche. Overexpression of Wnt3 is sufficient to increase neurogenesis from AHPs in vitro and in vivo. By contrast, blockade of Wnt signalling reduces neurogenesis from AHPs in vitro and abolishes neurogenesis almost completely in vivo. Our data show that Wnt signalling is a principal regulator of adult hippocampal neurogenesis and provide evidence that Wnt proteins have a role in adult hippocampal function.

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