Retinoic acid signalling regulates the development of tonotopically patterned hair cells in the chicken cochlea

Benjamin R. Thiede, Zoë F. Mann, Weise Chang, Yuan-Chieh Ku, Yena K. Son, Michael Lovett, Matthew W. Kelley and Jeffrey T. Corwin ()
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Benjamin R. Thiede: University of Virginia School of Medicine
Zoë F. Mann: Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health
Weise Chang: Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health
Yuan-Chieh Ku: Washington University School of Medicine
Yena K. Son: University of Virginia School of Medicine
Michael Lovett: Washington University School of Medicine
Matthew W. Kelley: Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health
Jeffrey T. Corwin: University of Virginia School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Precise frequency discrimination is a hallmark of auditory function in birds and mammals and is required for distinguishing similar sounding words, like ‘bat,’ ‘cat’ and ‘hat.’ In the cochlea, tuning and spectral separation result from longitudinal differences in basilar membrane stiffness and numerous individual gradations in sensory hair cell phenotypes, but it is unknown what patterns the phenotypes. Here we used RNA-seq to compare transcriptomes from proximal, middle and distal regions of the embryonic chicken cochlea, and found opposing longitudinal gradients of expression for retinoic acid (RA)-synthesizing and degrading enzymes. In vitro experiments showed that RA is necessary and sufficient to induce the development of distal-like hair cell phenotypes and promotes expression of the actin-crosslinking proteins, Espin and Fscn2. These and other findings highlight a role for RA signalling in patterning the development of a longitudinal gradient of frequency-tuned hair cell phenotypes in the cochlea.

Date: 2014
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DOI: 10.1038/ncomms4840

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