HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2008-0297v1 26/9/2311    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Angot, E. Articles by Traiffort, E. Search for Related Content PubMed PubMed Citation Articles by Angot, E. Articles by Traiffort, E.

THE STEM CELL NICHE

Chemoattractive Activity of Sonic Hedgehog in the Adult Subventricular Zone Modulates the Number of Neural Precursors Reaching the Olfactory Bulb

^aSignal Transduction and Developmental Neuropharmacology Team, Laboratoire de Neurobiologie Cellulaire et Moleculaire, Institut de Neurobiologie Alfred Fessard, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France;
^bUniversité Pierre et Marie Curie, Unité Mixte de Recherche 7102, Paris, France;
^cInstitut National de la Santé et de la Recherche Médicale, Unité 828, Pessac, France

Key Words. Hedgehog • Adult stem cell • Subventricular zone • Cell migration

Correspondence: Correspondence: Martial Ruat, Ph.D., Centre National de la Recherche Scientifique, Institut de Neurobiologie Alfred Fessard-IFR 2118, UPR9040, Laboratoire de Neurobiologie Cellulaire et Moleculaire, Signal Transduction and Developmental Neuropharmacology team, Batiment 33, 1 avenue de la Terrasse, F-91198, Gif-sur-Yvette, France. Telephone: 33169823641; Fax: 33169823639; e-mail: ruat{at}nbcm.cnrs-gif.fr

Received on March 26, 2008; accepted for publication on June 29, 2008.

First published online in STEM CELLS EXPRESS  July 10, 2008.

The adult subventricular zone (SVZ) supports neural stem cell self-renewal and differentiation and continually gives rise to new neurons throughout adult life. The mechanisms orienting the migration of neuroblasts from the SVZ to the olfactory bulb (OB) via the rostral migratory stream (RMS) have been extensively studied, but factors controlling neuroblast exit from the SVZ remain poorly explored. The morphogen Sonic Hedgehog (Shh) displays proliferative and survival activities toward neural stem cells and is an axonal chemoattractant implicated in guidance of commissural axons during development. We identify here the presence of Shh protein in SVZ extracts and in the cerebrospinal fluid of adult mice, and we demonstrate that migrating neuroblasts in the SVZ and RMS express the Shh receptor Patched. We show that Shh displays a chemoattractive activity in vitro on SVZ-derived neuronal progenitors, an effect blocked by Cur61414, a Smoothened antagonist. Interestingly, Shh-expressing cells grafted above the RMS of adult mice exert a chemoattractive activity on migrating neuroblasts in vivo, thus inducing their accumulation and deviation from their normal migratory pathway. Furthermore, the adenoviral transfer of Shh into the lateral ventricle or the blocking of Shh present in the SVZ of adult mice using its physiological antagonist Hedgehog interacting protein or neutralizing Shh antibodies provides in vivo evidence that Shh can retain SVZ-derived neuroblasts. The ability to modulate the number of neuroblasts leaving the SVZ and reaching the OB through the chemoattractive activity of Shh suggests a novel degree of plasticity in cell migration of this adult stem cell niche.

Disclosure of potential conflicts of interest is found at the end of this article.