ZFIN ID: ZDB-PUB-061227-44
Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch
Millimaki, B.B., Sweet, E.M., Dhason, M.S., and Riley, B.B.
Date: 2007
Source: Development (Cambridge, England)   134(2): 295-305 (Journal)
Registered Authors: Riley, Bruce, Sweet, Elly
Keywords: Hair cells, Proneural genes, Fgf, Delta-Notch, Pax2-5-8, Foxi1, Dlx, Msx, no isthmus (pax2a), mind bomb
MeSH Terms:
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors/genetics*
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • DNA/genetics
  • Ear, Inner/embryology*
  • Ear, Inner/metabolism*
  • Fibroblast Growth Factors/metabolism*
  • Gene Expression Regulation, Developmental
  • Hair Cells, Auditory/embryology
  • Hair Cells, Auditory/metabolism
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins/metabolism
  • Mice
  • Models, Biological
  • Mutation
  • PAX2 Transcription Factor/genetics
  • PAX2 Transcription Factor/metabolism
  • Paired Box Transcription Factors/genetics
  • Paired Box Transcription Factors/metabolism
  • Receptors, Notch/metabolism*
  • Signal Transduction
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 17166920 Full text @ Development
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.