Header

UZH-Logo

Maintenance Infos

Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells


Colak, D; Mori, T; Brill, M; Pfeifer, A; Falk, S; Deng, C; Monteiro, M; Mommery, C; Sommer, L; Götz, M (2008). Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells. Journal of Neuroscience, 283(2):434-446.

Abstract

In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cells and is crucial to initiate the neurogenic lineage in the adult mouse subependymal zone. Conditional deletion of Smad4 in adult neural stem cells severely impairs neurogenesis, and this is phenocopied by infusion of Noggin, an extracellular antagonist of BMP. Smad4 deletion in stem, but not progenitor cells, as well as Noggin infusion lead to an increased number of Olig2-expressing progeny that migrate to the corpus callosum and differentiate into oligodendrocytes. Transplantation experiments further verified the cell-autonomous nature of this phenotype. Thus, BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis.

Abstract

In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cells and is crucial to initiate the neurogenic lineage in the adult mouse subependymal zone. Conditional deletion of Smad4 in adult neural stem cells severely impairs neurogenesis, and this is phenocopied by infusion of Noggin, an extracellular antagonist of BMP. Smad4 deletion in stem, but not progenitor cells, as well as Noggin infusion lead to an increased number of Olig2-expressing progeny that migrate to the corpus callosum and differentiate into oligodendrocytes. Transplantation experiments further verified the cell-autonomous nature of this phenotype. Thus, BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis.

Statistics

Citations

162 citations in Web of Science®
169 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

237 downloads since deposited on 03 Feb 2009
46 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:03 Feb 2009 08:27
Last Modified:21 Nov 2017 13:54
Publisher:Society for Neuroscience
ISSN:0270-6474
Additional Information:Holder of copyright: The Society for Neuroscience
Publisher DOI:https://doi.org/10.1523/JNEUROSCI.4374-07.2008
PubMed ID:18184786

Download

Download PDF  'Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells'.
Preview
Filetype: PDF
Size: 1MB
View at publisher