Evolutionary conservation of sequence and expression of the bHLH protein Atonal suggests a conserved role in neurogenesis

Abstract

atonal is a Drosophila proneural gene that belongs to the family of basic helix-loop-helix (bHLH)- containing proteins. It is expressed in the chordotonal organs and photoreceptor cells, and flies that lack Atonal protein are ataxic and blind. Here we report the cloning of atonal homologs from red flour beetle, puffer fish, chicken, mouse, and human. The bHLH domain is conserved throughout evolution, while the entire coding region is highly similar in mammals. Both the chicken and the mouse homologs are expressed early in embryogenesis in the hind brain, and specifically in cells predicted to give rise to the external granular layer of the cerebellum. In addition, these genes are expressed throughout the dorsal part of the spinal cord, in patterns different from those found for other genes, like LH-2 and wnt-1. The mouse homolog (Math1) maps to mouse chromosome 6, and the human homolog (HATH1) to human chromosome 4q22. Two neurological mouse mutants, Lc and chp, were found to map to the vicinity of Math1, but are not caused by mutations in Math1. The evolutionary conservation of this gene and its mRNA expression patterns during embryogenesis suggests that it plays a key role in the development of the vertebrate central nervous system.