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

TY - JOUR

T1 - Retinoic acid signalling regulates the development of tonotopically patterned hair cells in the chicken cochlea

AU - Thiede, Benjamin R

AU - Chang, Weise

AU - Ku, Yuan-Chieh

AU - Son, Yena K

AU - Lovett, Michael

AU - Kelley, Matthew W

AU - Corwin, Jeffrey T

AU - Mann, Zoe

PY - 2014/5/20

Y1 - 2014/5/20

N2 - 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.

AB - 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.

KW - Aldehyde Oxidoreductases/genetics

KW - Animals

KW - Basilar Membrane/metabolism

KW - Carrier Proteins/genetics

KW - Chick Embryo

KW - Cytochrome P-450 Enzyme System/genetics

KW - Gene Expression Regulation, Developmental

KW - Hair Cells, Auditory/metabolism

KW - Microfilament Proteins/genetics

KW - RNA, Messenger/metabolism

KW - Receptors, Retinoic Acid/genetics

KW - Signal Transduction

KW - Tretinoin/metabolism

U2 - 10.1038/ncomms4840

DO - 10.1038/ncomms4840

M3 - Article

C2 - 24845860

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3840

ER -