Wnt signalling regulates adult hippocampal neurogenesis

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Abstract
Neural stem/progenitor cells in the adult brain are able to generate both the brain's major cell types: glial cells, which are non-neuronal, and the active nerve cells or neurons. Neurons are produced in just two regions of the brain. Lie et al. have now identified a protein family that instructs the adult neural stem cells to produce neurons, rather than glial cells. The signal molecule Wnt3 is shown to be crucial for the production of neurons in the adult hippocampus, a region believed to be involved in learning and memory formation. Ultimately these studies may help develop therapies to repair brain damage caused by disease or trauma. 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/β-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.