USC Scientists Uncover Key to Hearing Regeneration in Zebrafish and Lizards
A groundbreaking study by USC Stem Cell researchers has revealed how regenerative species like zebrafish and lizards restore hearing by reactivating dormant gene regulators. The findings could pave the way for treatments addressing hearing loss and balance disorders in humans.
The research, conducted by Tuo Shi, Ksenia Gnedeva, and Gage Crump from the Keck School of Medicine of USC, examined two crucial cell types in the inner ear: sensory cells, responsible for detecting sound, and supporting cells, which provide structural stability.
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By comparing regenerative vertebrates such as zebrafish and lizards to non-regenerative species like mice, the team discovered the pivotal role of DNA control elements known as enhancers. These enhancers, which boost the expression of specific genes, activate after injury in regenerative species, prompting the production of ATOH1, a protein essential for generating new sensory cells.
Using CRISPR gene-editing technology, the researchers removed five key enhancers in zebrafish. This resulted in significant developmental and regenerative impairments of sensory cells in the inner ear.
In contrast, while mice possess similar enhancers, these fail to remain active into adulthood, preventing mammals from regenerating damaged sensory cells.
Interestingly, the study noted that the genetic deletions in zebrafish affected sensory cells in their inner ear but left the lateral line—an organ specialized in detecting water movement—unaffected.
These findings provide new insights into the molecular mechanisms underlying hearing regeneration, offering hope for future therapies targeting hearing and balance disorders in humans.
