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The Journal of Neuroscience, February 15, 2001, 21(4):1265-1273
The Basic Helix-Loop-Helix Gene hesr2 Promotes Gliogenesis in Mouse Retina
Tetsu Satow1, 2, Soo-Kyung Bae1, Tomoyuki Inoue1, Chihiro Inoue1, Goichi Miyoshi1, Koichi Tomita1, Yasumasa Bessho1, Nobuo Hashimoto2, and Ryoichiro Kageyama1 1 Institute for Virus Research, Kyoto University, and 2 Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan
Members of a subclass of hairy/Enhancer of split [E(spl)] homologs, called hesr genes, are structurally related to another subclass of hairy/E(spl) homologs, Hes genes, which play an important role in neural development. To characterize the roles of hesr genes in neural development, we used the retina as a model system. In situ hybridization analysis indicated that all hesr genes are expressed in the developing retina, but only hesr2 expression is associated spatially with gliogenesis. Each member was then misexpressed with retrovirus in the retinal explant cultures prepared from mouse embryos or neonates, which well mimic in vivo retinal development. Interestingly, hesr2 but not hesr1 or hesr3 promoted gliogenesis while inhibiting rod genesis without affecting cell proliferation or death, suggesting that the cells that normally differentiate into rods adopted the glial fate by misexpression of hesr2. The gliogenic activity of hesr2 was more profound when it was misexpressed postnatally than prenatally. In addition, double mutation of the neuronal determination genes Mash1 and Math3, which increases Müller glia at the expense of bipolar cells, upregulated hesr2 expression. These results indicate that, among structurally related hesr genes, only hesr2 promotes glial versus neuronal cell fate specification in the retina and that antagonistic regulation between hesr2 and Mash1-Math3 may determine the ratios of neurons and glia.
Key words: bHLH; Müller glia; Hes; hesr; retina; retrovirus; rod
Copyright © 2001 Society for Neuroscience 0270-6474/01/2141265-09$05.00/0
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