Math6, a bHLH gene expressed in the developing nervous system, regulates neuronal versus glial differentiation.
BACKGROUND
Whereas multiple basic helix-loop-helix (bHLH) genes are expressed in the developing nervous system, they account for the differentiation of only subsets of neurones, suggesting that there may be as-yet unidentified bHLH genes.


RESULTS
We have isolated a novel bHLH gene, designated Math6, a distant mammalian homologue of the Drosophila proneural gene atonal. Structural analysis of the Math6 gene demonstrated that the coding region is divided into three exons, whereas that of other atonal homologues is present in a single exon, indicating that the genomic structure of Math6 is unique among the atonal homologues. Math6 is initially expressed by neural precursor cells in the ventricular zone, but later by subsets of differentiating and mature neurones such as hippocampal neurones and cerebellar Purkinje cells. Mis-expression of Math6 with retrovirus in the developing retina induced neurogenesis, while inhibiting gliogenesis, without affecting cell proliferation and death.


CONCLUSIONS
These results show that cells which would normally differentiate into glia adopted the neuronal fate by mis-expression of Math6, indicating that Math6 promotes neuronal vs. glial fate determination in the nervous system.
Inoue
C
C
Institute for Virus Research, Kyoto University, Department of Neurology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Bae
S K
SK
Takatsuka
K
K
Inoue
T
T
Bessho
Y
Y
Kageyama
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D012160:Retina / Q000196:embryology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C486727:ATOH8 protein, human; C449163:Atoh8 protein, mouse