The dlx5a gene is required for sensory cell regeneration in the inner ear of zebrafish larvae after injury
The dlx5a gene is required for sensory cell regeneration in the inner ear of zebrafish larvae after injury
On August 18, Nature Communications published a study of zebrafish larvae. The authors developed a model of inner ear injury, traced the origins of new hair cells, and tested the role of the dlx5a gene in their regeneration.
The vestibular system helps maintain balance. Its hair cells in the inner ear convert head rotation into neural signals. Damaged hair cells regenerate poorly in adult mammals, but they regenerate in zebrafish. Most experiments in zebrafish have examined the lateral line, a sensory organ on the body surface. In this study, the researchers examined the cristae of the semicircular canals, regions of the inner ear that detect head rotation.
In the study, the researchers injected the antibiotic neomycin directly into the inner ear vesicle of five-day-old larvae. The number of hair cells in the cristae of the semicircular canals fell by approximately 60%. New cells began to appear after 12 hours. After 48 hours, the vestibulo-ocular reflex had returned to the control level: when the body was rotated, the eyes again compensated for the movement.
The authors then traced the origins of the new cells. They labeled supporting cells, which are epithelial cells adjacent to hair cells. After injury, some labeled cells acquired hair cell features without visible cell division, while others divided first. A second fluorescent label showed that some regenerated hair cells arose from supporting cells that had themselves formed after the injury. In this model, new hair cells arise through several pathways.
To determine how gene activity changes during regeneration, the authors measured it in individual inner ear cells at 6, 24, and 48 hours after injury. They observed the largest changes in gene activity after 24 hours. In supporting cells, dlx5a stood out as a gene encoding a protein that regulates the activity of other genes. Its activity increased between 24 and 48 hours, then declined as the cells acquired hair cell features.
The authors used CRISPR–Cas9, a system that can disable a specified gene, to inactivate dlx5a in supporting cells. Hair cell regeneration was impaired after injury, while the number of hair cells remained at the usual level in uninjured larvae. In this model, supporting cells require dlx5a to regenerate hair cells after injury.