Wnt signalling regulates adult hippocampal neurogenesis.
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 gyrus. In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population. 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 development. We also show that the Wnt/beta-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.
Lie
Dieter-Chichung
DC
Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA. chichung.lie@gsf.de
Colamarino
Sophia A
SA
Song
Hong-Jun
HJ
Désiré
Laurent
L
Mira
Helena
H
Consiglio
Antonella
A
Lein
Edward S
ES
Jessberger
Sebastian
S
Lansford
Heather
H
Dearie
Alejandro R
AR
Gage
Fred H
FH
D000375:Aging / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060508:Wnt3 Protein
D012333:RNA, Messenger; D051153:Wnt Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse