A hairy regeneration problem

Scientists are starting to understand how zebrafish replace the cells that let them perceive vibrations – something mammals cannot do.

In the zebrafish lateral line, hair cells (shown in green) are regenerated from specific subsets of surrounding support cells (magenta): peripheral cells (left) do not contribute, while dorsoventral cells (right) make the majority of new hair cells. Image credit: Thomas and Raible (CC BY 4.0)

Deep inside our ears, tiny specialized cells called hair cells constantly detect and relay sound and spatial information to our brain. Without them, we lose our sense of hearing and balance. Unfortunately, the number of hair cells drops with age or after exposure to loud noises, and there is no way for our body to replace them. This can lead to permanent hearing and balance problems.

Zebrafish rely on similar hair cells to sense their environment. In particular, clusters of hair cells make up the lateral line system, an organ that helps fish perceive vibration and pressure in the water. However, unlike us, zebrafish can quickly and completely regenerate their hair cells. When these get damaged, surrounding ‘support cells’ divide to form new hair cells, but the details of this process were still vague. For example, it was unclear whether all support cells could create new hair cells, or only a certain population. There was also little evidence to show that support cells could regenerate themselves.

To investigate, Thomas and Raible used a precise genetic tool called CRISPR to label subsets of support cells that differed in their gene expression. Then, these cells were followed over time to see what they would become. This highlighted three distinct populations that played separate roles when hair cells were regenerated.

The support cells located at the top and bottom of the lateral line organs (dorsal and ventral cells) made most of the new hair cells. The cells located at the front and back (anterior and posterior cells) made a few; and the cells around the edges (peripheral cells) did not make any. Further experiments then showed that all three types of support cell could transform to replenish the stock of dorsal and ventral support cells that make new hair cells.

By being able to label and track precise groups of support cells, researchers will be able to dissect exactly how hair cells are regenerated in fish. Armed with this knowledge, it may become possible to explore ways to encourage human support cells to replace damaged hair cells in our ears.