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Atoh1 expression and function during auditory hair cell regeneration in post-hatch chickens
Rebecca M Lewis1, Clifford R Hume, Jennifer S Stone
1Department of Speech and Hearing Sciences, University of Washington, Seattle, WA 98195-7923, USA.
Hearing Research
|May 1, 2012
Summary
Hair cell regeneration in birds involves the transcription factor ATOH1. Inhibiting Notch signaling and overexpressing ATOH1 promote hair cell regeneration from supporting cells after damage.
Area of Science:
- Otolaryngology
- Regenerative Medicine
- Developmental Biology
Background:
- Human hearing loss is permanent due to the lack of auditory hair cell regeneration.
- Birds regenerate auditory hair cells from supporting cells via mitotic and non-mitotic pathways.
- The role of ATOH1 in hair cell regeneration is not fully understood.
Purpose of the Study:
- To investigate the expression and function of ATOH1 in chicken auditory hair cell regeneration.
- To determine if ATOH1 is sufficient for hair cell regeneration in damaged auditory epithelia.
Main Methods:
- Examined ATOH1 transcript levels in damaged chicken auditory epithelium.
- Utilized in vitro fate-mapping with an ATOH1 enhancer reporter.
- Inhibited Notch signaling using a gamma secretase antagonist.
- Forced overexpression of ATOH1 in supporting cells.
Main Results:
- ATOH1 transcripts increased in supporting cells post-damage, then localized to differentiating hair cells.
- Only 56% of supporting cells upregulating ATOH1 spontaneously became hair cells.
- Notch inhibition increased ATOH1 activity and hair cell differentiation to 73%.
- Forced ATOH1 expression induced hair cell fate in 66% of supporting cells and increased cell cycle entry.
Conclusions:
- ATOH1 is broadly upregulated in supporting cells after damage but does not guarantee hair cell fate.
- Gamma secretase-dependent Notch signaling partially inhibits ATOH1-mediated hair cell regeneration.
- ATOH1 is a key factor in hair cell regeneration, and its activity can be modulated by signaling pathways.
Related Concept Videos
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Hair Cells
Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
The Cochlea
The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.

