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The Journal of Neuroscience, December 17, 2003, 23(37):11732-11740

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Development/Plasticity/Repair
A Novel Secretory Factor, Neurogenesin-1, Provides Neurogenic Environmental Cues for Neural Stem Cells in the Adult Hippocampus

Takatoshi Ueki,¹ Masamitsu Tanaka,^2,4 Kanna Yamashita,¹ Sumiko Mikawa,¹ ZheFu Qiu,¹ Nicholas J. Maragakis,⁵ Robert F. Hevner,⁶ Naoyuki Miura,³ Haruhiko Sugimura,² and Kohji Sato¹

¹Department of Anatomy and Neuroscience, ²First Department of Pathology, and ³Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan, ⁴Growth Factor Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan, ⁵Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, and ⁶Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98104

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.

Key words: Neurogenesin-1; astrocyte; neural stem cell; rat; hippocampus; neurogenesis; neurogenic cues

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Received May 26, 2003; revised October 21, 2003; accepted October 22, 2003.

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