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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
Journal article   Open access   Peer reviewed

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

Wei Pan, Ying Jin, Jing Chen, Robbert J Rottier, Karen P Steel and Amy E Kiernan
The Journal of neuroscience, v 33(41), pp 16146-16157
09 Oct 2013
DOI: https://doi.org/10.1523/JNEUROSCI.3150-12.2013
PMID: 24107947
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1523/JNEUROSCI.3150-12.2013View
Published, Version of Record (VoR) Open

Abstract

Animals Cell Differentiation - physiology Ear, Inner - cytology Ear, Inner - metabolism Immunohistochemistry Mice Mice, Transgenic Microscopy, Electron, Scanning Neural Stem Cells - cytology Neural Stem Cells - metabolism Receptors, Notch - metabolism Signal Transduction - physiology SOXB1 Transcription Factors - metabolism
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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Neurosciences
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