Journal article
Ectopic expression of activated notch or SOX2 reveals similar and unique roles in the development of the sensory cell progenitors in the mammalian inner ear
The Journal of neuroscience, v 33(41), pp 16146-16157
09 Oct 2013
PMCID: PMC3792456
PMID: 24107947
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hearing impairment or vestibular dysfunction in humans often results from a permanent loss of critical cell types in the sensory regions of the inner ear, including hair cells, supporting cells, or cochleovestibular neurons. These important cell types arise from a common sensory or neurosensory progenitor, although little is known about how these progenitors are specified. Studies have shown that Notch signaling and the transcription factor Sox2 are required for the development of these lineages. Previously we and others demonstrated that ectopic activation of Notch can direct nonsensory cells to adopt a sensory fate, indicating a role for Notch in early specification events. Here, we explore the relationship between Notch and SOX2 by ectopically activating these factors in nonsensory regions of the mouse cochlea, and demonstrate that, similar to Notch, SOX2 can specify sensory progenitors, consistent with a role downstream of Notch signaling. However, we also show that Notch has a unique role in promoting the proliferation of the sensory progenitors. We further demonstrate that Notch can only induce ectopic sensory regions within a certain time window of development, and that the ectopic hair cells display specialized stereocilia bundles similar to endogenous hair cells. These results demonstrate that Notch and SOX2 can both drive the sensory program in nonsensory cells, indicating these factors may be useful in cell replacement strategies in the inner ear.
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Details
- Title
- Ectopic expression of activated notch or SOX2 reveals similar and unique roles in the development of the sensory cell progenitors in the mammalian inner ear
- Creators
- Wei Pan - University of RochesterYing Jin - 1Department of Ophthalmology andJing Chen - Wellcome Sanger InstituteRobbert J Rottier - Erasmus MC - Sophia Children’s HospitalKaren P Steel - Wellcome Sanger InstituteAmy E Kiernan - University of Rochester
- Publication Details
- The Journal of neuroscience, v 33(41), pp 16146-16157
- Publisher
- Society for Neuroscience
- Grant note
- Wellcome Trust G0300212 / Medical Research Council 100669 / Wellcome Trust R01 DC009250 / NIDCD NIH HHS DC009250 / NIDCD NIH HHS MC_QA137918 / Medical Research Council 098051 / Wellcome Trust
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000325644800010
- Scopus ID
- 2-s2.0-84885111628
- Other Identifier
- 991020545121704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences