Ybx1 acts upstream of Atoh1a to promote the rapid regeneration of hair cells in zebrafish lateral-line neuromasts
Like the sensory organs of the human inner ear, the lateral-line neuromasts of fish such as the zebrafish Danio rerio contain mechanosensory hair cells that are surrounded by progenitors called supporting cells. Damaged neuromasts can quickly regenerate new hair cells by expressing in the progenitors hair cell-specific genes such as Atoh1a, the master regulator of hair cell fate. We used the supervised-learning algorithm DELAY to infer regenerating neuromasts' early gene-regulatory network and to identify adaptations that promote the rapid regeneration of lateral-line hair cells in larval zebrafish. The central hub in the network, Y box-binding protein 1 (Ybx1), is highly expressed in hair cell progenitors and young hair cells and can recognize DNA-binding motifs in cyprinids’ candidate regeneration-responsive promoter elements for Atoh1a. We showed that neuromasts from ybx1 mutant zebrafish larvae display consistent, regeneration-specific deficits in hair cell number and initiate both hair cell regeneration and Atoh1a expression 20% slower than in siblings. By demonstrating that Ybx1 promotes rapid hair cell regeneration through early upregulation of Atoh1a, the results support DELAY’s ability to identify novel temporal regulators of gene expression.
A schematic diagram portrays the regulation of atoh1a expression before the ablation of hair acells, in an early phase of the response by Ybx1, and at a later phase of hair cell regeneration in mechanosensory neuromasts of the zebrafish’s posterior lateral line
