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Nestin Regulates Neurogenesis in Mice Through Notch Signaling From Astrocytes to Neural Stem Cells

Journal article
Authors Ulrika Wilhelmsson
Isabell Lebkuechner
Renata Leke
Pavel Marasek
Xiaoguang Yang
D. Antfolk
Meng Chen
P. Mohseni
E. Lasic
S. T. Bobnar
M. Stenovec
R. Zorec
A. Nagy
C. Sahlgren
Marcela Pekna
Milos Pekny
Published in Cerebral Cortex
Volume 29
Issue 10
Pages 4050-4066
ISSN 1047-3211
Publication year 2019
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 4050-4066
Language en
Links dx.doi.org/10.1093/cercor/bhy284
Subject categories Neurosciences

Abstract

The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes(-/-)) mice. We found that the proliferation of Nes(-/-) neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes(-/-) mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.

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