Fluorescence images of ybx1 mutant neuromasts [Ybx1 immunofluorescence]

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 progenitors called
supporting cells. Damaged NMs can quickly regenerate new HCs by expressing
in the progenitors HC-specific genes such as atoh1a, the master regulator
of HC fate. We used the supervised learning algorithm DELAY to infer
regenerating NMs' early gene-regulatory network (GRN) and identify
adaptations that promote the rapid regeneration of lateral-line HCs in
larval zebrafish. The central hub in the network, Y-box binding protein 1
(ybx1), is highly expressed in HC progenitors and young HCs and can
recognize DNA-binding motifs in cyprinids' candidate
regeneration-responsive promoter elements 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 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.