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

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Article numberbio059911
Number of pages13
JournalBiology open
Issue number6
Publication statusPublished - 15 Jun 2023

External IDs

unpaywall 10.1242/bio.059911
WOS 001042144100001
ORCID /0000-0002-3274-7163/work/142249712
ORCID /0000-0003-0283-0211/work/142257356
Scopus 85187652965


Subject groups, research areas, subject areas according to Destatis


  • CRISPR/Cas9, Development, Inner ear, Transcriptome analysis, Zebrafish, Humans, Ear, Inner/metabolism, Gene Expression Profiling, Transcription Factors/genetics, Zebrafish/genetics, Zebrafish Proteins/genetics, Animals, Homeodomain Proteins/genetics

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