The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse retina.
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.
Satow
T
T
Institute for Virus Research, Kyoto University, and Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Bae
S K
SK
Inoue
T
T
Inoue
C
C
Miyoshi
G
G
Tomita
K
K
Bessho
Y
Y
Hashimoto
N
N
Kageyama
R
R
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins; D016923:Cell Death; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005804:Genes, Lethal; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D019476:Insect Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D012097:Repressor Proteins; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism* / Q000821:virology; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C120390:Hey protein, Drosophila; C485778:Hey2 protein, mouse; C104516:Neurod4 protein, mouse