A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear

Mann, Zoë F.; Thiede, Benjamin R.; Chang, Weise; Shin, Jung-Bum; May-Simera, Helen; Lovett, Michael; Corwin, Jeffrey T.; Kelley, Matthew W.

doi:10.1038/ncomms4839

Cited by 36 publications

(79 citation statements)

References 56 publications

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“…In the chick, Mann and colleagues propose that noncanonical BMP signalling is a key mechanism in establishing the tonotopic organisation of the cochlea [36 ].…”

Section: Sensory Hair Cell Differentiation and Cochlear Tonotopymentioning

confidence: 99%

Development of the inner ear

Whitfield¹

2015

Current Opinion in Genetics & Development

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The vertebrate inner ear is a sensory organ of exquisite design and sensitivity. It responds to sound, gravity and movement, serving both auditory (hearing) and vestibular (balance) functions. Almost all cell types of the inner ear, including sensory hair cells, sensory neurons, secretory cells and supporting cells, derive from the otic placode, one of the several ectodermal thickenings that arise around the edge of the anterior neural plate in the early embryo. The developmental patterning mechanisms that underlie formation of the inner ear from the otic placode are varied and complex, involving the reiterative use of familiar signalling pathways, together with roles for transcription factors, transmembrane proteins, and extracellular matrix components. In this review, I have selected highlights that illustrate just a few of the many recent discoveries relating to the development of this fascinating organ system.

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“…In the chick, Mann and colleagues propose that noncanonical BMP signalling is a key mechanism in establishing the tonotopic organisation of the cochlea [36 ].…”

Section: Sensory Hair Cell Differentiation and Cochlear Tonotopymentioning

confidence: 99%

Development of the inner ear

Whitfield¹

2015

Current Opinion in Genetics & Development

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“…The apical to basal gradient of Bmp7 signaling was recently shown to determine tonotopic organization of hair cells in explants of BP (6). We investigated Bmp7 expression in our in vivo Shh model and found that Bmp7 expression levels are evidently increased in the basal and middle regions in Shh-beadimplanted ears ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These morphological and physiological features of the cochlea are conferred by a large number of genes that are differentially expressed along the developing cochlea (3)(4)(5)(6)(7). Notably, two signaling molecules, bone morphogenetic protein 7 (Bmp7) and retinoic acid (RA), were recently demonstrated to be important for establishing some of the tonotopic features of the BP (6,7).…”

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confidence: 99%

“…Notably, two signaling molecules, bone morphogenetic protein 7 (Bmp7) and retinoic acid (RA), were recently demonstrated to be important for establishing some of the tonotopic features of the BP (6,7). Sequential apical-to-basal expression gradients of Bmp7 and Raldh3 (encoding the RA synthesizing enzyme, retinaldehyde dehydrogenase 3) appear to confer apical identity in the BP (6) and apical hair cell morphology (7), respectively. However, several important questions remain about the development of the tonotopic organization of the cochlea: (i) What is the signaling pathway(s) upstream of Bmp7 and RA?…”

mentioning

confidence: 99%

“…These morphological changes are preceded by expansion of apically expressed genes toward the base of the papilla including Bmp7, which has been demonstrated to mediate some of the tonotopic features described here (6). We also examined a gain-of-Shh function mouse model, Pax2…”

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Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea

Son¹,

Hyun

Ankamreddy

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Sound frequency discrimination begins at the organ of Corti in mammals and the basilar papilla in birds. Both of these hearing organs are tonotopically organized such that sensory hair cells at the basal (proximal) end respond to high frequency sound, whereas their counterparts at the apex (distal) respond to low frequencies. Sonic hedgehog (Shh) secreted by the developing notochord and floor plate is required for cochlear formation in both species. In mice, the apical region of the developing cochlea, closer to the ventral midline source of Shh, requires higher levels of Shh signaling than the basal cochlea farther away from the midline. Here, gain-of-function experiments using Shh-soaked beads in ovo or a mouse model expressing constitutively activated Smoothened (transducer of Shh signaling) show up-regulation of apical genes in the basal cochlea, even though these regionally expressed genes are not necessarily conserved between the two species. In chicken, these altered gene expression patterns precede morphological and physiological changes in sensory hair cells that are typically associated with tonotopy such as the total number of stereocilia per hair cell and gene expression of an inward rectifier potassium channel, IRK1, which is a bona fide feature of apical hair cells in the basilar papilla. Furthermore, our results suggest that this conserved role of Shh in establishing cochlear tonotopy is initiated early in development by Shh emanating from the notochord and floor plate.frequency discrimination | regional identity | Inhba | A2m | Efnb2

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Cochlear tonotopy from proteins to perception

Fettiplace

2023

BioEssays

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A ubiquitous feature of the auditory organ in amniotes is the longitudinal mapping of neuronal characteristic frequencies (CFs), which increase exponentially with distance along the organ. The exponential tonotopic map reflects variation in hair cell properties according to cochlear location and is thought to stem from concentration gradients in diffusible morphogenic proteins during embryonic development. While in all amniotes the spatial gradient is initiated by sonic hedgehog (SHH), released from the notochord and floorplate, subsequent molecular pathways are not fully understood. In chickens, BMP7 is one such morphogen, secreted from the distal end of the cochlea. In mammals, the developmental mechanism differs from birds and may depend on cochlear location.A consequence of exponential maps is that each octave occupies an equal distance on the cochlea, a spacing preserved in the tonotopic maps in higher auditory brain regions. This may facilitate frequency analysis and recognition of acoustic sequences.

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A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear

Cited by 36 publications

References 56 publications

Development of the inner ear

Development of the inner ear

Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea

Cochlear tonotopy from proteins to perception

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