Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch.
Hair cells of the inner ear develop from an equivalence group marked by expression of the proneural gene Atoh1. In mouse, Atoh1 is necessary for hair cell differentiation, but its role in specifying the equivalence group (proneural function) has been questioned and little is known about its upstream activators. We have addressed these issues in zebrafish. Two zebrafish homologs, atoh1a and atoh1b, are together necessary for hair cell development. These genes crossregulate each other but are differentially required during distinct developmental periods, first in the preotic placode and later in the otic vesicle. Interactions with the Notch pathway confirm that atoh1 genes have early proneural function. Fgf3 and Fgf8 are upstream activators of atoh1 genes during both phases, and foxi1, pax8 and dlx genes regulate atoh1b in the preplacode. A model is presented in which zebrafish atoh1 genes operate in a complex network leading to hair cell development.
Millimaki
Bonny B
BB
Biology Department, Texas A&M University, College Station, TX 77843-3258, USA.
Sweet
Elly M
EM
Dhason
Mary S
MS
Riley
Bruce B
BB
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000196:embryology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D005346:Fibroblast Growth Factors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051762:PAX2 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D051880:Receptors, Notch; D014157:Transcription Factors; D029961:Zebrafish Proteins; C500943:Atoh1 protein, mouse; C514187:Atoh1a protein, zebrafish; C494467:Pax8 protein, zebrafish; C500361:atoh1b protein, zebrafish; C064045:delta protein; C497320:pax2a protein, zebrafish