PUBLICATION

Transcriptome analysis reveals an Atoh1b-dependent gene set downstream of Dlx3b/4b during early inner ear development in zebrafish

Authors
Ezhkova, D., Schwarzer, S., Spieß, S., Geffarth, M., Machate, A., Zöller, D., Stucke, J., Alexopoulou, D., Lesche, M., Dahl, A., Hans, S.
ID
ZDB-PUB-230606-30
Date
2023
Source
Biology Open   12(6): (Journal)
Registered Authors
Geffarth, Michaela, Hans, Stefan, Machate, Anja, Zöller, Daniela
Keywords
CRISPR/Cas9, Development, Inner ear, Transcriptome analysis, Zebrafish
Datasets
GEO:GSE220565, GEO:GSE220564
MeSH Terms
  • Animals
  • Ear, Inner*/metabolism
  • Gene Expression Profiling
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Humans
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics
PubMed
37272628 Full text @ Biol. Open
Abstract
The vertebrate inner ear is the sensory organ mediating hearing and balance. The entire organ develops from the otic placode, which itself originates from the otic-epibranchial progenitor domain (OEPD). Multiple studies in various species have shown the importance of the forkhead-box and distal-less homeodomain transcription factor families for OEPD and subsequent otic placode formation. However, the transcriptional networks downstream of these factors are only beginning to be understood. Using transcriptome analysis, we here reveal numerous genes regulated by the distal-less homeodomain transcription factors Dlx3b and Dlx4b (Dlx3b/4b). We identify known and novel transcripts displaying widespread OEPD expression in a Dlx3b/4b-dependent manner. Some genes, with a known OEPD expression in other vertebrate species, might be members of a presumptive vertebrate core module required for proper otic development. Moreover, we identify genes controlling early-born sensory hair cell formation as well as regulating biomineral tissue development, both consistent with defective sensory hair cell and otolith formation observed in dlx3b/4b mutants. Finally, we show that ectopic Atoh1b expression can rescue early sensorigenesis even in the absence of Dlx3b/4b. Taken together, our data will help to unravel the gene regulatory network underlying early inner ear development and provide insights into the molecular control of vertebrate inner ear formation to restore hearing loss in humans ultimately.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping