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Nat Neurosci. 2014 Jul;17(7):943-52. doi: 10.1038/nn.3732. Epub 2014 May 25.

ALK5-dependent TGF-β signaling is a major determinant of late-stage adult neurogenesis.

Author information

1
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
2
Department of Biology, Stanford University, Stanford, California, USA.
3
Present address: The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, USA (S.A.V.), Department of Bioengineering, University of California San Diego, La Jolla, California, USA, and Department of Medicine, University of California San Diego, La Jolla, California, USA (P.A.J.).
4
1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2] Center for Tissue Regeneration, Repair and Rehabilitation, VA Palo Alto Health Care System, Palo Alto, California, USA.

Abstract

The transforming growth factor-β (TGF-β) signaling pathway serves critical functions in CNS development, but, apart from its proposed neuroprotective actions, its physiological role in the adult brain is unclear. We observed a prominent activation of TGF-β signaling in the adult dentate gyrus and expression of downstream Smad proteins in this neurogenic zone. Consistent with a function of TGF-β signaling in adult neurogenesis, genetic deletion of the TGF-β receptor ALK5 reduced the number, migration and dendritic arborization of newborn neurons. Conversely, constitutive activation of neuronal ALK5 in forebrain caused a marked increase in these aspects of neurogenesis and was associated with higher expression of c-Fos in newborn neurons and with stronger memory function. Our findings describe an unexpected role for ALK5-dependent TGF-β signaling as a regulator of the late stages of adult hippocampal neurogenesis, which may have implications for changes in neurogenesis during aging and disease.

PMID:
24859199
PMCID:
PMC4096284
DOI:
10.1038/nn.3732
[Indexed for MEDLINE]
Free PMC Article
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