title: Sox2 and Fgf interact with Atoh1 to promote sensory competence throughout the zebrafish inner ear.
abstract: Atoh1 is required for differentiation of sensory hair cells in the vertebrate inner ear. Moreover, misexpression of Atoh1 is sufficient to establish ectopic sensory epithelia, making Atoh1 a good candidate for gene therapy to restore hearing. However, competence to form sensory epithelia appears to be limited to discrete regions of the inner ear. To better understand the developmental factors influencing sensory-competence, we examined the effects of misexpressing atoh1a in zebrafish embryos under various developmental conditions. Activation of a heat shock-inducible transgene, hs:atoh1a, resulted in ectopic expression of early markers of sensory development within 2h, and mature hair cells marked by brn3c:GFP began to accumulate 9h after heat shock. The ability of atoh1a to induce ectopic sensory epithelia was maximal when activated during placodal or early otic vesicle stages but declined rapidly thereafter. At no stage was atoh1a sufficient to induce sensory development in dorsal or lateral non-sensory regions of the otic vesicle. However, co-misexpression of atoh1a with fgf3, fgf8 or sox2, genes normally acting in the same gene network with atoh1a, stimulated sensory development in all regions of the otic vesicle. Thus, expression of fgf3, fgf8 or sox2 strongly enhances competence to respond to Atoh1.
authors.affiliation: Biology Department, Texas A&M University, College Station, TX 77843-3258, USA.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Sweet
authors.forename: Shruti
authors.initials: S
authors.lastname: Vemaraju
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Riley
mesh_terms: D000818:Animals; D007758:Ear, Inner / Q000196:embryology / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000502:physiology*; D017403:In Situ Hybridization; D055747:SOX Transcription Factors / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C514187:Atoh1a protein, zebrafish; D055747:SOX Transcription Factors; C544611:Sox2 protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors