| First Author | Savoy-Burke G | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 9 | Pages | e108160 |
| PubMed ID | 25264928 | Mgi Jnum | J:223490 |
| Mgi Id | MGI:5649210 | Doi | 10.1371/journal.pone.0108160 |
| Citation | Savoy-Burke G, et al. (2014) Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells. PLoS One 9(9):e108160 |
| abstractText | PURPOSE: To determine whether activated Notch can promote a supporting cell fate during sensory cell differentiation in the inner ear. METHODS: An activated form of the Notch1 receptor (NICD) was expressed in early differentiating hair cells using a Gfi1-Cre mouse allele. To determine the effects of activated Notch on developing hair cells, Gfi1-NICD animals and their littermate controls were assessed at 5 weeks for hearing by measuring auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). The differentiation of NICD-expressing hair cells was assessed at postnatal day (P) 6, 11 and 20, using histological and molecular markers for hair cells, as well as supporting cells/progenitor cells. We also examined whether the effects of Notch were mediated by SOX2, a gene expressed in supporting cells and a likely downstream target of Notch, by crossing an inducible form of SOX2 to the Gfi1-Cre. RESULTS: Activation of Notch1 in developing auditory hair cells causes profound deafness. The NICD-expressing hair cells switch off a number of hair cell markers and lose their characteristic morphology. Instead, NICD-expressing hair cells adopt a morphology resembling supporting cells and upregulate a number of supporting cell markers. These effects do not appear to be mediated by SOX2, because although expression of SOX2 caused some hearing impairment, the SOX2-expressing hair cells did not downregulate hair cell markers nor exhibit a supporting cell-like phenotype. CONCLUSIONS: Our data show that Notch signaling inhibits hair cell differentiation and promotes a supporting cell-like phenotype, and that these effects are unlikely to be mediated by SOX2. |
