A recent study by USC Stem Cell scientists revealed how certain regenerative species, such as zebrafish and lizards, restore hearing by reactivating dormant gene regulators.
This discovery has shed light on potential mechanisms that could help humans recover from hearing loss and balance disorders.
The research, led by Tuo Shi, Ksenia Gnedeva, and Gage Crump from the Keck School of Medicine of USC, focused on two critical cell types in the inner ear: sensory cells, which detect sound, and supporting cells, which provide structural support.
By comparing regenerative vertebrates like zebrafish and lizards to non-regenerative vertebrates such as mice, the team identified the fundamental role of DNA control elements called “enhancers” in replacing sensory cells after damage.
These enhancers, which amplify the expression of specific genes, activated after injury in regenerative species, triggering the production of ATOH1, a protein that initiates the creation of new sensory cells.
Using CRISPR, researchers deleted five key enhancers in zebrafish, leading to significant impairments in both the development of sensory cells during embryonic stages and their regeneration after damage.
Mice were found to possess similar enhancers that function during embryonic development but lose the ability to maintain them in an open configuration into adulthood. This loss prevents the regeneration of damaged sensory cells in mammals.
The study further showed that genetic deletions affected sensory cells in the zebrafish's inner ear but left its lateral line, an organ specialized for detecting water movement, unaffected.
