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Researchers Discover a Type of Supporting Cells Resistant to Notch Signaling

In a new study in the January 20 issue of Developmental Cell, House Ear Institute (HEI) researchers have shown that by blocking a biochemical pathway called the Notch signaling pathway, most of the supporting cells in the inner ear of juvenile mice are induced to directly change into hair cells.

“Interestingly, the new study has shown that all supporting cells do not behave the same, and so some cells may be more amenable to regenerative therapies than others,” said Neil Segil, Ph.D., a senior author and principal investigator at House Ear Institute.

Specifically, one type of supporting cells, the so-called pillar cells, are resistant to the loss of Notch signaling. So, even when Notch signaling is blocked, pillar cells do not turn into hair cells.

While sensory hair cells in the inner ear (cochlea) of birds and other lower vertebrates have the ability to regenerate after being deafened, the sensory hair cells in the cochlea of humans and other mammals cannot. The causes of this failure of regeneration has long been the holy grail in the world of hearing loss research. Currently, there is no cure for sensorineural hearing loss, whose widespread occurrence is largely the result of damage to the cochlea’s sensory hair cells from injury, aging, certain medications or infection.

In a study reported in Nature in June 2006, House Ear Institute (HEI) researchers discovered that some cells in the mouse inner ear known as supporting cells, like their counterparts in birds and reptiles, are able to turn into hair cells, at least for a short time after birth. This discovery gave new hope to the quest for regenerative therapies for hearing loss. However, the mechanisms underlying the change from supporting cell into hair cell, the basis of regeneration in birds and reptiles, remains unknown.

Pillar cells are a highly specialized supporting cell type that matures to form the tunnel of Corti in the inner ear and are essential for cochlear function. In the organ of Corti, the pillar cells are located between the inner and outer hair cells.

Researchers determined that the resistance to loss of Notch signaling is caused by a gene known as Hey2, which is present in the pillar cells, and is necessary for pillar cells resisting turning into hair cells. Hey2 is a member of a family of genes, and the data suggests that other members of this family are present in different supporting cell types in the early postnatal organ of Corti and help define different subpopulations of supporting cells, with Hey2 defining pillar cells.

Also reported for the first time in this study, the team identified FGF, fibroblast growth factor, as a regulation factor for Hey2 in pillar cells. The researchers hypothesize that FGF released from inner hair cells maintains Hey2 expression and contributes to the establishment of the pillar cell region, which divides inner from outer hair cells, a crucial function in a developing ear.

This newly described function of Hey2 in resisting the loss of Notch signaling is likely to influence the thinking about the role of this important biochemical pathway in many other developing embryonic cell types, such as the segmental development of the spinal column, and the differentiation of the cells of the brain.

Segil along with co-author Andy Groves, Ph.D., associate professor of neuroscience and genetics at Baylor College of Medicine, and lead author Angelika Doetzlhofer, Ph.D., think that the role of Hey2 may help explain some of the evolutionary changes that have occurred in the inner ear of vertebrates, such as the existence of multiple rows of pillar cells in our distant relatives the duck-billed platypus. These same mechanisms may help explain how the separation of the inner and outer hair cells is maintained and possibly how these cell types were able to evolve independently.

About the House Ear Institute

The House Ear Institute (HEI) is a non-profit 501(c)(3) organization dedicated to advancing hearing science through research and education to improve quality of life. HEI scientists investigate the cellular and molecular causes of hearing loss and related auditory disorders as well as neurological processes pertaining to the human auditory system and the brain. Our researchers also explore technology advancements to improve auditory implants, hearing aids, diagnostic techniques and rehabilitation tools. The Institute shares its knowledge with the scientific and medical communities as well as the general public through its education and outreach programs.

Kirsten Holguin | Newswise Science News
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