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Multi-scale analysis of the interplay between cell morphology and cell-cell signaling

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From hair cells to hearing loss

New discoveries about how inner ear hair cells are formed could open the door to developing therapeutic approaches to treating hearing loss.

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What do embryos, hair cells and hearing have to do with one another? Turns out, a lot. “Humans develop hair cells in our inner ear as embryos,” says David Sprinzak, a researcher at Tel Aviv University. As Sprinzak explains, these inner ear hair cells are highly specialised cells that are responsible for turning sound vibrations into electrical signals. These signals are then conveyed to the brain, which essentially translates them into the sounds we hear. Unfortunately, as we grow older, we begin to lose these hair cells and, with it, some of our ability to hear properly. But this could soon change, thanks in part to the work being done by the EU-funded MorphoNotch project. The project, which is being spearheaded by Sprinzak’s Lab and received support from the European Research Council, is working to better understand the processes that cause hair cells to form during embryonic development. “If we know how these hair cells are formed, we might be able to regenerate them as a means of treating, if not preventing, hearing loss,” explains Sprinzak.

A focus on Notch signalling

At the heart of the project is the effort to understand how hair cells in the inner ear form a precise pattern of four rows during embryonic development. According to Sprinzak, this cellular pattern is important for the function of the inner ear. “We wanted to understand how such an important and complex structure emerges during embryonic development,” he says. To do so, the research team focused on Notch signalling, the primary pathway for coordinating the differentiation between neighbouring cells in animals. “In particular, we looked at the interplay between Notch signalling and the mechanical forces that control the development of the mammalian inner ear,” adds Sprinzak.

How cells organise during embryonic development

What the project found is that Notch signalling controls the formation of an initially disordered pattern of hair cells. However, these cells eventually reorganise into an ordered pattern in a process that is analogous to the formation of a crystal, a process typically observed in atomic physics. “This discovery represents a new developmental mechanism for how cells organise during embryonic development,” remarks Sprinzak. But perhaps the project’s most important finding was that these two processes, the differentiation of hair cells controlled by Notch signalling and the reorganisation of cells controlled by mechanical forces, are intimately coupled. “I am very proud of this discovery because we were able to identify a fundamental process that has implications in the development of many other tissues and organs,” explains Sprinzak.

New therapeutic approaches to treating hearing loss

With this fundamental understanding of how hair cells are formed, Sprinzak is now turning his attention to studying regenerative approaches to hearing loss. “Hair cell regeneration in the inner ear is an exciting field that focuses on developing methods to induce the regeneration of sensory hair cells,” he adds. Sprinzak is confident that the concepts introduced during the MorphoNotch project will play a fundamental role in this field. “Our findings have the potential to contribute to the development of new therapeutic approaches to treating hearing loss,” he concludes.

Keywords

MorphoNotch, hair cells, hearing loss, inner ear, embryonic development, Notch signalling

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