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 expres sed in the developing nervous system, they account for the differentiation of only subsets of neurones, suggesting that there may be as-yet unidentifi ed bHLH genes. Results: We have isolated a novel bHLH gene, designated Math6, a distant ma mmalian homologue of the Drosophila proneural gene atonal. Structural analy sis of the Math6 gene demonstrated that the coding region is divided into t hree exons, whereas that of other atonal homologues is present in a single exon, indicating that the genomic structure of Math6 is unique among the at onal homologues. Math6 is initially expressed by neural precursor cells in the ventricular zone, but later by subsets of differentiating and mature ne urones such as hippocampal neurones and cerebellar Purkinje cells. Mis-expr ession of Math6 with retrovirus in the developing retina induced neurogenes is, while inhibiting gliogenesis, without affecting cell proliferation and death. Conclusions: These results show that cells which would normally differentia te into glia adopted the neuronal fate by mis-expression of Math6, indicati ng that Math, promotes neuronal vs. glial fate determination in the nervous system.