ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs

Developmental Biology
Mark E WarcholMichael Lovett

Abstract

The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also...Continue Reading

References

Sep 8, 2001·Journal of the Association for Research in Otolaryngology : JARO·P J LanfordM W Kelley
Nov 12, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Norio YamamotoTasuku Honjo
May 29, 2007·Developmental Biology·Shinji TakebayashiTasuku Honjo
Feb 23, 2008·Developmental Biology·Toshinori HayashiOlivia Bermingham-McDonogh
Aug 21, 2008·The Journal of Biological Chemistry·Jeremy Pak Hong ChowMasaharu Noda
May 11, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael C KellyPing Chen
Aug 31, 2013·Journal of the Association for Research in Otolaryngology : JARO·Amber D Slowik, Olivia Bermingham-McDonogh
Jul 21, 2015·Developmental Cell·Andrés Romero-CarvajalTatjana Piotrowski

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Citations

Jul 19, 2018·ELife·Ruth Rebecca TaylorAndrew Forge
Sep 27, 2018·Cold Spring Harbor Perspectives in Medicine·Amanda S Janesick, Stefan Heller
Dec 4, 2019·Stem Cell Research & Therapy·Cheng ChengRenjie Chai

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