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PMID: 18160632 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Mosaic removal of hedgehog signaling in the adult SVZ reveals that the residual wild-type stem cells have a limited capacity for self-renewal.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 52 ·2007-12-26 ·Pages 14248-59

Balordi F, Fishell G

Abstract

The Smoothened gene is necessary for cells to transduce hedgehog signaling. Although we and others have previously shown that embryonic removal of Smoothened in the neural tube results in a loss of stem cells from the postnatal subventricular zone, it was unclear whether this reflected a requirement for hedgehog signaling in the establishment or maintenance of the adult niche. Here, we have examined the consequences of conditional removal of Smoothened gene function within the subventricular zone of the adult neural stem cell niche. We observe that both proliferation and neurogenesis are compromised when hedgehog signaling is removed from subventricular zone stem cells. Moreover, even after a 10 month survival period, the stem cell niche fails to recover. It has been reported that the adult subventricular zone quickly rebounds from an antimitotic insult by increasing proliferation and replenishing the niche. During this recovery, it has been reported that hedgehog signaling appears to be upregulated. When mice in which hedgehog signaling in the subventricular zone has been strongly attenuated are given a similar antimitotic treatment, recovery is limited to the reduced level of proliferation and neurogenesis observed before the mitotic insult. Furthermore, the limited recovery that is observed appears to be largely restricted to the minority of neural stem cells that escape the conditional inactivation of Smoothened gene function. These results demonstrate that ongoing hedgehog signaling is required to maintain adult neural stem cells and that their ability to self-renew is limited.

MeSH Terms
Adult Stem Cells/drug effects,physiology Animals Bromodeoxyuridine/metabolism Cell Differentiation/drug effects,physiology Cell Proliferation/drug effects Cytoskeletal Proteins/metabolism Embryo, Mammalian Estrogen Antagonists/pharmacology Hedgehog Proteins/metabolism In Vitro Techniques Integrases/physiology Intermediate Filament Proteins/genetics Lateral Ventricles/cytology Luminescent Proteins/genetics,metabolism Mice Mice, Transgenic Nerve Tissue Proteins/genetics,metabolism Nestin Receptors, Estrogen/genetics Receptors, G-Protein-Coupled/physiology Signal Transduction/physiology Smoothened Receptor Stem Cell Transplantation/methods Tamoxifen/pharmacology
Chemicals
Cytoskeletal Proteins Estrogen Antagonists Hedgehog Proteins Intermediate Filament Proteins Luminescent Proteins Nerve Tissue Proteins Nes protein, mouse Nestin Receptors, Estrogen Receptors, G-Protein-Coupled Smo protein, mouse Smoothened Receptor activity regulated cytoskeletal-associated protein Tamoxifen Cre recombinase Integrases Bromodeoxyuridine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Balordi Francesca
Smilow Neuroscience Program and the Department of Cell Biology, Smilow Research Center, New York University School of Medicine, New York, New York 10016, USA.
Fishell Gord
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4531-07.2007
Published
2007-12-26
Pages
14248-59
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6673442
Subset
IM
Grants
NINDS NIH HHS · R01NS039007 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4531-07.2007 PMC Full Text View journal details
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