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Atoh1 in sensory hair cell development: constraints and cofactors.

TitleAtoh1 in sensory hair cell development: constraints and cofactors.
Publication TypeJournal Article
Year of Publication2017
AuthorsCosta A, Powell LM, Lowell S, Jarman AP
JournalSemin Cell Dev Biol
Volume65
Pagination60-68
Date Published2017 05
ISSN1096-3634
KeywordsAnimals, Basic Helix-Loop-Helix Transcription Factors, Caenorhabditis elegans, Cell Differentiation, DNA-Binding Proteins, Drosophila melanogaster, Gene Expression Regulation, Developmental, Hair Cells, Auditory, Homeodomain Proteins, Mechanoreceptors, Mechanotransduction, Cellular, Mice, Organ Specificity, Transcription Factor Brn-3C, Transcription Factors
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.

DOI10.1016/j.semcdb.2016.10.003
Alternate JournalSemin. Cell Dev. Biol.
PubMed ID27751776
Grant ListMR/L021099/1 / / Medical Research Council / United Kingdom
103789/Z/14/Z / / Wellcome Trust / United Kingdom
Publication institute
CRM