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Hearing Research
Article
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Hearing Research
Article . 2013 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Beyond generalized hair cells: Molecular cues for hair cell types

Authors: Israt, Jahan; Ning, Pan; Jennifer, Kersigo; Bernd, Fritzsch;

Beyond generalized hair cells: Molecular cues for hair cell types

Abstract

Basic helix-loop-helix (bHLH) transcription factors (TFs) are crucial for inner ear neurosensory development. The proneural TF Atoh1 regulates the differentiation of hair cells (HCs) whereas Neurog1 and Neurod1 regulate specification and differentiation of neurons, respectively, but also affect HC development. Expression of Delta and Jagged ligands in nascent HCs and Notch receptors in supporting cells induce supporting cell differentiation through the regulation of neurogenic bHLH TFs (such as Hes1, Hes5) and suppression of limited Atoh1 expression. In sensorineural hearing loss, HCs are lost followed by supporting cells and progressive degeneration of neurons, at least in rodents. Regaining complete hearing may require reconstituting the organ of Corti from scratch, including the two types of HCs, inner and outer hair cells with the precise sorting of two types of afferent (type I and II) and efferent (lateral and medial olivo-cochlear) innervation. We review effects of bHLH TF dosage and their cross-regulation to differentiate HC types in the organ of Corti. We categorize findings of specific gene expressions in HCs: 1. as markers without meaning for the regeneration task, 2. as stabilizers who are needed to maintain or complete differentiation, and 3. as decision-making genes, expressed and acting early enough to be useful in this process. Only one TF has been characterized that fits the last aspect: Atoh1. We propose that temporal and intensity variations of Atoh1 are naturally modulated to differentiate specific types of HCs. Importantly, the molecular means to modify the Atoh1 expression are at least partially understood and can be readily implemented in the attempts to regenerate specific types of HCs.

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Keywords

Neurons, Gene Expression Regulation, Developmental, Cell Differentiation, Mice, Transgenic, Nerve Tissue Proteins, Cochlea, Nerve Regeneration, Mice, Hair Cells, Auditory, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Organ of Corti

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
43
Top 10%
Top 10%
Top 10%
bronze