title: Molecular cloning and functional characterisation of chicken Atonal homologue 1: a comparison with human Atoh1.
abstract: BACKGROUND
  The vertebrate basic helix-loop-helix transcription factor Atoh1 is essential for maturation and survival of mechanosensory hair cells of the inner ear, neurogenesis, differentiation of the intestine, homeostasis of the colon and is implicated in cancer progression. Given that mutations in Atoh1 are detected in malignant tumours, study of functionally different Atoh1 alleles and homologues might yield useful avenues for investigation. The predicted sequence of chicken Atoh1 (cAtoh1) has large regions of dissimilarity to that of mammalian Atoh1 homologues. We hypothesise that cAtoh1 might have intrinsic functional differences to mammalian Atoh1.
  
  
  RESULTS
  In this study, we cloned and sequenced the full open reading frame of cAtoh1. In overexpression experiments, we show that this sequence is sufficient to generate a cAtoh1 protein capable of inducing hair cell markers when expressed in nonsensory regions of the developing inner ear, and that morpholino-mediated knock-down using a section of the sequence 5' to the start codon inhibits differentiation of hair cells in the chicken basilar papilla. Furthermore, we compare the behaviour of cAtoh1 and human Atoh1 (hAtoh1) in embryonic mouse cochlear explants, showing that cAtoh1 is a potent inducer of hair cell differentiation and that it can overcome Sox2-mediated repression of hair cell differentiation more effectively than hAtoh1.
  
  
  CONCLUSIONS
  cAtoh1 is both necessary and sufficient for avian mechanosensory hair cell differentiation. The non-conserved regions of the cAtoh1 coding region have functional consequences on its behaviour.
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada.
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Mulvaney
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Amemiya
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Freeman
authors.forename: Raj K
authors.initials: RK
authors.lastname: Ladher
authors.forename: Alain
authors.initials: A
authors.lastname: Dabdoub
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002645:Chickens / Q000235:genetics*; D003001:Cloning, Molecular; D003051:Cochlea / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007760:Labyrinth Supporting Cells / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D030161:Avian Proteins; D015415:Biomarkers; D055748:SOXB1 Transcription Factors
keywords: Cochlea; Development; Notch; Regeneration; cAtoh1