title: Atoh1 in sensory hair cell development: constraints and cofactors.
abstract: The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum. The reasons for this context dependence are poorly understood. So far, the pathways and key players that instruct Atoh1 to act as a mechanosensory cell fate determinant in the context of the inner ear are largely unknown. Here we review evidence that suggests that Atoh1 function in hair cell differentiation is modulated by interaction with other transcription factors. We particularly focus on the possible roles of Gfi1 and Pou4f3, drawing from studies in mouse, Drosophila and C. elegans.
authors.affiliation: Centre for Integrative Physiology, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK; MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK. Electronic address: aida.costa@ed.ac.uk.
authors.forename: Aida
authors.initials: A
authors.lastname: Costa
authors.affiliation: Centre for Integrative Physiology, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK. Electronic address: lynn.powell@ed.ac.uk.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Powell
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK. Electronic address: sally.lowell@ed.ac.uk.
authors.forename: Sally
authors.initials: S
authors.lastname: Lowell
authors.affiliation: Centre for Integrative Physiology, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK. Electronic address: andrew.jarman@ed.ac.uk.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jarman
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008465:Mechanoreceptors / Q000166:cytology / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D051379:Mice; D009928:Organ Specificity; D050821:Transcription Factor Brn-3C / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C079873:Gfi1 protein, mouse; C121290:Pou4f3 protein, mouse
keywords: Cochlea; Development; Hair cell; Mechanosensory; Transcription factor