What Do a Leather Pouch and a Fruit Fly Have in Common?

By Yishane Lee

What is the utricle? Merriam-Webster defines it as “a small anatomical pouch; the part of the membranous labyrinth of the inner ear into which the semicircular canals open.” But to you and me, it may help provide the solution to hair cell regeneration in the inner ear.

Like the cochlea, the utricle is located in the inner ear and it contains hair cells that are used to detect gravity (versus the sound waves that the cochlear hair cells detect). In a major step forward, Hearing Restoration Project scientist Dr. Jennifer Stone and her colleagues at the University of Washington pioneered the technique of isolating the utricle from the adult mouse and growing it in a dish in the lab.

Why is this important? It is providing for the first time the ability to directly access and experimentally manipulate hair cells and support cells in a lab setting. In other words, we can grow and do experiments on the utricle (a word derived from the Latin for leather bag). The cochlea has proven to be too delicate to isolate and grow in a dish.

As Dr. Andy Groves, Baylor College of Medicine, and an HRP colleague writes in the Winter 2014 issue of Hearing Health:

“Dr. Stone’s lab found that within a few days after hair cells are killed in the utricle, the surrounding supporting cells take the very first genetic steps to activate the program to make hair cells—but then they stop before the hair cells actually form. It is as though the supporting cells have received a signal to regenerate new hair cells, but they cannot ‘seal the deal’ and complete the regeneration program. This situation is very different from the cochlea, where absolutely no hair cell regeneration steps occur in adults.”

Drs. Grove and Stone, along with Dr. Neil Segil of the University of Southern California, are working together to figure out why regeneration takes the first steps and then stops. One area they are focusing on is the Notch signaling pathway, an evolutionarily determined method of cell communication. Notch signaling, among other things, determines the mosaic patterns of various cell types, including the mosaic that organizes the inner ear’s hair cells and supporting cells. The dysfunction of Notch signaling (a name that comes from a notch found in the wings of a fruit fly) has been linked to various cancers and diseases, and as a result it has become a focus of drug intervention.

Read about all of our HRP projects here, and stay tuned for more HRP updates throughout the year.

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