Adult Neurogenesis Requires Smad4-mediated Bone Morphogenic Protein Signaling in Stem Cells

Overview

Journal J Neurosci

Specialty Neurology

Date 2008 Jan 11

PMID 18184786

Citations 118

Authors

Dilek Colak

Tetsuji Mori

Monika S Brill

Alexander Pfeifer

Sven Falk

Chuxia Deng

Rui Monteiro

Christine Mummery

Lukas Sommer

Magdalena Gotz

Affiliations

Soon will be listed here.

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.

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