ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs
Autor: | Jennifer S. Stone, Michael Lovett, Mark E. Warchol, Nicolas Daudet, Matthew Barton, Jeffrey Ku, Rose Veile |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cellular differentiation Cell Notch signaling pathway Chick Embryo Biology Article ADAM10 Protein Hair Cells Vestibular 03 medical and health sciences Organ Culture Techniques otorhinolaryngologic diseases medicine Animals Regeneration Inner ear Saccule and Utricle Molecular Biology Vestibular Hair Cell Cell Proliferation Receptors Notch Cell growth Cell Differentiation Epithelial Cells Cell Biology Anatomy Cell cycle Cell biology 030104 developmental biology medicine.anatomical_structure sense organs Hair cell Amyloid Precursor Protein Secretases Chickens Developmental Biology |
Zdroj: | Developmental Biology. 428:39-51 |
ISSN: | 0012-1606 |
Popis: | 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 trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration. |
Databáze: | OpenAIRE |
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