TY - JOUR T1 - The Basic Helix-Loop-Helix Gene <em>hesr2</em> Promotes Gliogenesis in Mouse Retina JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1265 LP - 1273 DO - 10.1523/JNEUROSCI.21-04-01265.2001 VL - 21 IS - 4 AU - Tetsu Satow AU - Soo-Kyung Bae AU - Tomoyuki Inoue AU - Chihiro Inoue AU - Goichi Miyoshi AU - Koichi Tomita AU - Yasumasa Bessho AU - Nobuo Hashimoto AU - Ryoichiro Kageyama Y1 - 2001/02/15 UR - http://www.jneurosci.org/content/21/4/1265.abstract N2 - Members of a subclass of hairy/Enhancer of split [E(spl)] homologs, calledhesr 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 allhesr 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 orhesr3 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 ofhesr2 was more profound when it was misexpressed postnatally than prenatally. In addition, double mutation of the neuronal determination genes Mash1 andMath3, which increases Müller glia at the expense of bipolar cells, upregulated hesr2 expression. These results indicate that, among structurally related hesrgenes, 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. ER -