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The way that hair cells in the zebrafish sensory system regenerate after damage or death may help us figure out how to treat hearing loss, according to a new study in Developmental Cell.

"The sensory hair cells in the zebrafish lateral line are homologous to mammalian inner ear sensory hair cells, however, the lateral line is experimentally accessible because it is located in the skin of the fish. In contrast to mammals, fish, reptiles, birds and amphibians regenerate their sensory hair cells. We can learn what the genetic basis of this regeneration is and then hopefully apply it one day to trigger regeneration in mammals," Tatjana Piotrowski, Ph.D., Research Associate Investigator at the Stowers Institute for Medical Research, told ALN exclusively.

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The research team treated zebrafish larvae with an antibiotic that kills hair cells. For the next three days, they monitored support cell proliferation using time-lapse movies. They focused, in particular, on the regeneration of neuroblasts, which are garlic-shaped sensory organs.

They found that around half of the dividing support cells differentiated into hair cells, while the rest self-renewed, forming a reserve force. The fate of the support cells depended on where they were located in the neuromast. Self-renewing cells were found at oppposite poles, while the differentiating cells were found close to the center.

The researchers also studied the gene and signaling pathways involved. "We showed that quiescence, self-renewal, and differentiation of fish sensory hair cells occur in distinct organ compartments, regulated by localized Notch  and Wnt signaling interactions," Dr. Piotrowski added. Self-renewal cells required Wnt signaling and is inhibited by Notch, whereas differentiation is signaled by Notch.

The researchers hope these findings will lead to treatments that reverse hearing loss. "Understanding the molecular mechanisms (signaling pathways) that regulate sensory hair cell regeneration in the zebrafish will help us to a) elucidate why mammals do not regenerate sensory hair cells (the surrounding cells do not proliferate) and b) hopefully will enable us to trigger a regenerative response in mammals in the future," Dr. Piotrowski concluded.

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