In contrast to species which continually generate new hair cells, humans are among the mammals that just can’t hack it. Once hair cells die from ageing or after prolonged noise exposure, they do not regenerate.

But what if scientists could make that happen? It’s a long way off, but some important clues to how as to how this process might be encouraged are appearing from within a lab – Piotrowski Lab – set up at the Stowers Institute for Medical Research in Kansas City, USA. This specific laboratory, aided by funding from the Hearing Health Foundation and institutional support from Stower, has turned square on to examine our old friend the zebrafish, whose lateral line develops from a group of around 100 cells, the primordium, formed from the fish’s ear down towards the tail tip, depositing sensory organs, called neuromasts, along the way. Hair cells similar to those in mammalian ears develop in these neuromasts extending cilia that detect movements in water in ways similar to how mammals’ ears detect sound waves in the air.

 

Two specific genes could lead to activation of cell regeneration pathways in humans

 

The proliferation of cells needed to replace those dying or damaged only happens if there are existing cells that can divide, so the regulation of this proliferation has become the focus of study involving genetic manipulation, carried out with the aim of ascertaining which specific genes are important for regeneration.

A key discovery was reported by scientists at Stowers this summer of 2025 – in the journal Nature Communications – namely that the biological mechanisms in zebrafish cell regeneration involve two specific cyclinD genes. CyclinD genes also regulate cell division in human tissues such as the gut and blood.

By manipulating these genes, making one non-functional, and by engineering them to work in different ways, it was established that different groups of cells within an organ can be controlled separately. Though highly complex, especially in expression and signalling, the cyclins looked at in zebrafish produced results to demonstrate that “proliferation of zebrafish lateral line stem and progenitor cells is independently regulated, with potentially important implications for our understanding of how, in other organs and species, the proliferation of quiescent and activated stem cells and their daughter cells can be manipulated when diseased”.

The Piotrowski team says it is hopeful their research will elucidate how zebrafish hair cells regenerate, and this has implications for hair cell regeneration in mammals that might pave the way for treatments for hearing loss.

 

Why zebrafish?

 

It is the transparency of zebrafish during their development that makes them apt for this research. Their sensory organ systems are accessible, allowing scientists to visualise and genetically modify each neuromast cell. They can then explore stem cell renewal and the process leading to hair cell regeneration.

 

Sources: Nature Communications/Piotrowski Lab