title: Molecular characterization and mapping of ATOH7, a human atonal homolog with a predicted role in retinal ganglion cell development.
abstract: The human ATOH7 gene encodes a basic helix-loop-helix (bHLH) transcription factor that is highly similar to Drosophila Atonal within the conserved bHLH domain. The ATOH7 coding region is contained within a single exon. We mapped ATOH7 to Chromosome (Chr) 10q21.3-22.1, a region syntenic to the segment of mouse Chr 10 where Atoh7 (formerly Math5) is located. The evolutionary relationship between ATOH7 and other atonal homologs was investigated using parsimony analysis. A direct comparison of ATH5/7 and ATH1 protein subgroups to Atonal also revealed a nonrandom distribution of amino acid changes across the bHLH domain, which may be related to their separate visual and proprioceptive sensory functions. Among bHLH genes, ATOH7 is most closely related to Atoh7. This sequence conservation extends significantly beyond the coding region. We define blocks of strong homology in flanking human and mouse genomic DNA, which are likely to include cis regulatory elements. Because targeted deletion of Atoh7 causes optic nerve agenesis in mice, we propose ATOH7 as a candidate for human optic nerve aplasia and related clinical syndromes.
authors.affiliation: Department of Pediatrics at Children's Memorial Institute for Education and Research, Northwestern University Medical School, Chicago, Illinois 60614-3394, USA.
authors.forename: Nadean L
authors.initials: NL
authors.lastname: Brown
authors.forename: Susan L
authors.initials: SL
authors.lastname: Dagenais
authors.forename: Chuan-Min
authors.initials: CM
authors.lastname: Chen
authors.forename: Tom
authors.initials: T
authors.lastname: Glaser
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010802:Phylogeny; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D017422:Sequence Analysis, DNA; D026801:Synteny; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C500942:ATOH1 protein, human; C456975:ATOH7 protein, human; C500943:Atoh1 protein, mouse; C117638:Atoh7 protein, mouse