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

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.

Development of the inner ear

“…Moreover, manipulation of Bmp signalling by over-expression of either Bmp7 or Chordin-like1 abolished gradients of hair cell density and morphology as expected [36 ]. A second RNA-seq transcriptome analysis has highlighted the graded expression of genes coding for RA-synthesising or RA-degrading enzymes along the developing cochlea in the chick [37 ].…”

Where hearing starts: the development of the mammalian cochlea

“…; Thiede et al. ). In birds, the proximal region of the basilar papilla responses to higher frequencies similar to the basal part of the mammalian organ of Corti, while distal regions respond to lower frequencies, similar to the apical organ of Corti.…”

Fate‐mapping analysis using Rorb‐IRES‐Cre reveals apical‐to‐basal gradient of Rorb expression in mouse cochlea

“…3 The inner ear SE typically contains mechanosensitive receptors, the hair cells (HCs) and neighboring supporting cells (SCs); however, the HCs and SCs in each individual present unique morphological and geneexpression profiles. [8][9][10] Moreover, the distinct developmental properties of the HCs and SCs at each cochlear turn contribute to the tonotopic axis. The mammalian cochlea harbors two types of HCs, outer HCs (OHCs) and inner HCs (IHCs), which are, respectively, sound amplifiers and primary sensory cells.…”