Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells.
To determine whether activated Notch can promote a supporting cell fate during sensory cell differentiation in the inner ear.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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4180070?pdf=render |
| _version_ | 1818313549774061568 |
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| author | Grace Savoy-Burke Felicia A Gilels Wei Pan Diana Pratt Jianwen Que Lin Gan Patricia M White Amy E Kiernan |
| author_facet | Grace Savoy-Burke Felicia A Gilels Wei Pan Diana Pratt Jianwen Que Lin Gan Patricia M White Amy E Kiernan |
| author_sort | Grace Savoy-Burke |
| collection | DOAJ |
| description | To determine whether activated Notch can promote a supporting cell fate during sensory cell differentiation in the inner ear.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.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.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. |
| first_indexed | 2024-12-13T08:35:31Z |
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| id | doaj.art-ed274ad044c94e6f8edff9cad611d2c5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T08:35:31Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ed274ad044c94e6f8edff9cad611d2c52022-12-21T23:53:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10816010.1371/journal.pone.0108160Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells.Grace Savoy-BurkeFelicia A GilelsWei PanDiana PrattJianwen QueLin GanPatricia M WhiteAmy E KiernanTo determine whether activated Notch can promote a supporting cell fate during sensory cell differentiation in the inner ear.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.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.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.http://europepmc.org/articles/PMC4180070?pdf=render |
| spellingShingle | Grace Savoy-Burke Felicia A Gilels Wei Pan Diana Pratt Jianwen Que Lin Gan Patricia M White Amy E Kiernan Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells. PLoS ONE |
| title | Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells. |
| title_full | Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells. |
| title_fullStr | Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells. |
| title_full_unstemmed | Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells. |
| title_short | Activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells. |
| title_sort | activated notch causes deafness by promoting a supporting cell phenotype in developing auditory hair cells |
| url | http://europepmc.org/articles/PMC4180070?pdf=render |
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