Reagor Caleb C, Bravo Paloma, Hudspeth A J
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York, NY, United States of America.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
PeerJ. 2025 Sep 16;13:e19949. doi: 10.7717/peerj.19949. eCollection 2025.
Like the sensory organs of the human inner ear, the lateral-line neuromasts (NMs) of fish such as the zebrafish () 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 , 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, (), 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 . We showed that NMs from mutant zebrafish larvae display consistent, regeneration-specific deficits in HC number and initiate both HC regeneration and expression 20% slower than in wild-type siblings. By demonstrating that promotes rapid HC regeneration through early upregulation, the results support DELAY's ability to identify key temporal regulators of gene expression.