PUBLICATION
ybx1 acts upstream of atoh1a to promote the rapid regeneration of hair cells in zebrafish lateral-line neuromasts
- Authors
- Reagor, C.C., Bravo, P., Hudspeth, A.J.
- ID
- ZDB-PUB-250923-5
- Date
- 2025
- Source
- PeerJ 13: e19949e19949 (Journal)
- Registered Authors
- Hudspeth, A.J. (Jim)
- Keywords
- Gene-regulatory network, Hair cell regeneration, Machine learning, atoh1a, ybx1
- MeSH Terms
-
- Basic Helix-Loop-Helix Transcription Factors*/genetics
- Basic Helix-Loop-Helix Transcription Factors*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Lateral Line System*/cytology
- Lateral Line System*/metabolism
- Lateral Line System*/physiology
- Regeneration*/genetics
- Animals
- Larva
- Y-Box-Binding Protein 1*/genetics
- Y-Box-Binding Protein 1*/metabolism
- Hair Cells, Auditory*/metabolism
- Hair Cells, Auditory*/physiology
- Zebrafish*/genetics
- PubMed
- 40980064 Full text @ Peer J.
Citation
Reagor, C.C., Bravo, P., Hudspeth, A.J. (2025) ybx1 acts upstream of atoh1a to promote the rapid regeneration of hair cells in zebrafish lateral-line neuromasts. PeerJ. 13:e19949e19949.
Abstract
Like the sensory organs of the human inner ear, the lateral-line neuromasts (NMs) of fish such as the zebrafish (Danio rerio) contain mechanosensory hair cells (HCs) that are surrounded by supporting cells (SCs). A damaged NM can quickly regenerate new HCs by expressing genes such as atoh1a, the master regulator of HC fate, in the SCs at the NM's center. We used the supervised learning algorithm DELAY to infer the early gene-regulatory network for regenerating central SCs and HCs and identified adaptations that promote the rapid regeneration of lateral-line HCs in larval zebrafish. The top hub in the network, Y-box binding protein 1 (ybx1), is highly expressed in HC progenitors and young HCs and its protein can recognize DNA-binding motifs in cyprinids' candidate regeneration-responsive promoter element for atoh1a. We showed that NMs from ybx1 mutant zebrafish larvae display consistent, regeneration-specific deficits in HC number and initiate both HC regeneration and atoh1a expression 20% slower than in wild-type siblings. By demonstrating that ybx1 promotes rapid HC regeneration through early atoh1a upregulation, the results support DELAY's ability to identify key temporal regulators of gene expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping