A novel secretory factor, Neurogenesin-1, provides neurogenic environmental cues for neural stem cells in the adult hippocampus

Neurogenesis occurs in restricted regions in the adult mammalian brain, among which the neurogenesis in the hippocampal dentate gyrus plays the crucial role in learning and memory. To date, little is known about neurogenic cues, which result in the neuronal fate adoption of neural stem cells residin...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-12, Vol.23 (37), p.11732-11740
Main Authors: Ueki, Takatoshi, Tanaka, Masamitsu, Yamashita, Kanna, Mikawa, Sumiko, Qiu, ZheFu, Maragakis, Nicholas J, Hevner, Robert F, Miura, Naoyuki, Sugimura, Haruhiko, Sato, Kohji
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Astrocytes - metabolism
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins - antagonists & inhibitors
Brain - anatomy & histology
Brain - cytology
Brain - embryology
Cell Differentiation
Cells, Cultured
Cloning, Molecular
Development/Plasticity/Repair
Ectoderm - cytology
Hippocampus - cytology
Hippocampus - metabolism
Male
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Neurons - cytology
Neurons - metabolism
Protein Structure, Tertiary
Rats
Rats, Wistar
RNA, Messenger - metabolism
Sequence Alignment
Stem Cells - physiology
Xenopus
Xenopus Proteins
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Summary:Neurogenesis occurs in restricted regions in the adult mammalian brain, among which the neurogenesis in the hippocampal dentate gyrus plays the crucial role in learning and memory. To date, little is known about neurogenic cues, which result in the neuronal fate adoption of neural stem cells residing in neurogenic regions, especially neurogenic cues in adult hippocampal neurogenesis. In the present study, we show that hippocampal astrocytes and also dentate granule cells adjacent to neural stem cells secrete a newly cloned novel secretory factor, Neurogenesin-1. This protein contains three cysteine-rich domains and a unique sequence and contributes to neuronal differentiation of neural stem cells in the adult brain by preventing the adoption of a glial fate. Furthermore, the neurogenic activity detected in the hippocampal culture medium was markedly suppressed by the administration of an anti-Neurogenesin-1 antibody. These findings suggest endogenous mechanisms that induce adult hippocampal neurogenesis and propose an innovative treatment for the neurodegenerative diseases that cause loss of hippocampal neurons.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.23-37-11732.2003