Gene Expression by Mouse Inner Ear Hair Cells during Development

Scheffer, Déborah I.; Shen, Jun; Corey, David P.; Chen, Zhengyi

doi:10.1523/jneurosci.5126-14.2015

Cited by 276 publications

(359 citation statements)

References 62 publications

Supporting

Mentioning

333

Contrasting

Order By: Relevance

“…Those studies have provided evidence that connexin-related (Cx26 and Cx30) gap junction channels in supporting cells mediate K + recycling and absorption [3,10]. However, recent transcriptomic analyses of hair cells show that Gjb2 (encoding Cx26) and Gjb6 (encoding Cx30), which are components of gap junction channels and crucial cellular structures during development, are also highly expressed in embryonic and adult hair cells [49, 55, 56]. Therefore, it is possible that deletion of Gjb2 or Gjb6 may directly lead to abnormal hair cell development and/or death.…”

Section: Discussionmentioning

confidence: 99%

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Liu

Chen

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Liu

Chen

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…In one report that examines both proteins, Atoh1 and Gfi1 were found to be co-expressed in cochlear inner hair cells as early as E15.0, and in outer hair cells by E15.5 (76). Transcriptome analyses also support their coexpression during later stages of differentiation (77). The earliest expression of Atoh1 in the cochlea is around E13.5, a time when Gfi1 is not yet detectable (10).…”

Section: How Might Atoh1 and Gfi1 Interact?mentioning

confidence: 96%

Atoh1 in sensory hair cell development: constraints and cofactors

Costa

Powell

Lowell

et al. 2017

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum. The reasons for this context dependence are poorly understood. So far, the pathways and key players that instruct Atoh1 to act as a mechanosensory cell fate determinant in the context of the inner ear are largely unknown. Here we review evidence that suggests that Atoh1 function in hair cell differentiation is modulated by interaction with other transcription factors. We particularly focus on the possible roles of Gfi1 and Pou4f3, drawing from studies in mouse, Drosophila and C. elegans.3

show abstract

“…While initially used primarily to characterize the level of expression of mRNAs in the wild type tissue, it was later used to identify complex gene networks, decipher regulatory pathways and characterize response to various stimuli. Numerous studies have profiled the inner ear gene expression using microarray technology, focusing on model organisms such as mouse and zebrafish, both in normal and pathological conditions (Hertzano and Elkon, 2012; Scheffer et al, 2015). In contrast to the wealth of data available for model organisms, very little is known about gene expression in the human inner ear, mainly due to difficulties in obtaining the relevant tissues.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear

et al. 2016

View full text Add to dashboard Cite

The mammalian inner ear consists of the cochlea and the vestibular labyrinth (utricle, saccule, and semicircular canals), which participate in both hearing and balance. Proper development and life-long function of these structures involves a highly complex coordinated system of spatial and temporal gene expression. The characterization of the inner ear transcriptome is likely important for the functional study of auditory and vestibular components, yet, primarily due to tissue unavailability, detailed expression catalogues of the human inner ear remain largely incomplete. We report here, for the first time, comprehensive transcriptome characterization of the adult human cochlea, ampulla, saccule and utricle of the vestibule obtained from patients without hearing abnormalities. Using RNA-Seq, we measured the expression of >50,000 predicted genes corresponding to approximately 200,000 transcripts, in the adult inner ear and compared it to 32 other human tissues. First, we identified genes preferentially expressed in the inner ear, and unique either to the vestibule or cochlea. Next, we examined expression levels of specific groups of potentially interesting RNAs, such as genes implicated in hearing loss, long non-coding RNAs, pseudogenes and transcripts subject to nonsense mediated decay (NMD). We uncover the spatial specificity of expression of these RNAs in the hearing/balance system, and reveal evidence of tissue specific NMD. Lastly, we investigated the non-syndromic deafness loci to which no gene has been mapped, and narrow the list of potential candidates for each locus. These data represent the first high-resolution transcriptome catalogue of the adult human inner ear. A comprehensive identification of coding and non-coding RNAs in the inner ear will enable pathways of auditory and vestibular function to be further defined in the study of hearing and balance. Expression data are freely accessible at https://www.tgen.org/home/research/research-divisions/neurogenomics/supplementary-data/inner-ear-transcriptome.aspx

show abstract

Gene Expression by Mouse Inner Ear Hair Cells during Development

Cited by 276 publications

References 62 publications

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Atoh1 in sensory hair cell development: constraints and cofactors

A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear

Contact Info

Product

Resources

About