NEX-1: a Novel Brain-specific Helix-loop-helix Protein with Autoregulation and Sustained Expression in Mature Cortical Neurons

Mutations affecting peripheral nervous system development in Drosophila and mouse indicate that neural differentiation depends on the coordinated expression of cell type-specific bHLH proteins. We have identified a novel bHLH gene, termed NEX-1, which is expressed exclusively and abundantly in the mammalian central nervous system. By in situ hybridization, induction of the rodent NEX-1 gene coincides with the generation of postmitotic neurons and parallels overt neuronal differentiation and synaptogenesis. Unexpected for bHLH proteins, NEX-1 may play a role in neuronal function throughout adult life. High levels of its mRNA are sustained in mature pyramidal neurons of the hippocampus, cerebellum and several neocortical areas previously associated with learning and memory formation. When ectopically expressed in PC12 cells, NEX-1 transactivates the promoter of its own gene. This suggests that positive autoregulation stabilizes the activity of NEX-1 and its target genes in subsets of mature neurons.