Retinoic acid signalling regulates the development of tonotopically patterned hair cells in the chicken cochlea.
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.
Department of Neuroscience, University of Virginia School of Medicine, 409 Lane Road, Charlottesville, Virginia 22908, USA.
Benjamin R
BR
Thiede
Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 35A Convent Drive, Bethesda, Maryland 20892-3729, USA.
Zoë F
ZF
Mann
Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 35A Convent Drive, Bethesda, Maryland 20892-3729, USA.
Weise
W
Chang
Division of Human Genetics, Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Yuan-Chieh
YC
Ku
Department of Neuroscience, University of Virginia School of Medicine, 409 Lane Road, Charlottesville, Virginia 22908, USA.
Yena K
YK
Son
Division of Human Genetics, Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Michael
M
Lovett
Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 35A Convent Drive, Bethesda, Maryland 20892-3729, USA.
Matthew W
MW
Kelley
1] Department of Neuroscience, University of Virginia School of Medicine, 409 Lane Road, Charlottesville, Virginia 22908, USA [2] Department of Cell Biology, University of Virginia School of Medicine, 409 Lane Road, Charlottesville, Virginia 22908, USA.
Jeffrey T
JT
Corwin
D000445:Aldehyde Oxidoreductases / Q000235:genetics; D000818:Animals; D001489:Basilar Membrane / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*
D002352:Carrier Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; C020324:fascin; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+)