Neuronal cell adhesion molecule (NrCAM) is expressed by sensory cells in the cochlea and is necessary for proper cochlear innervation and sensory domain patterning during development

Harley, Randall J.; Murdy, Joseph P.; Wang, Zhirong; Kelly, Michael C.; Ropp, Tessa-Jonne F.; Park, Sehoon H.; Maness, Patricia F.; Manis, Paul B.; Coate, Thomas M.

doi:10.1002/dvdy.24629

Cited by 15 publications

(18 citation statements)

References 75 publications

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“…1). Previously, we documented how cochlear morphology and ribbon synapse distribution were able to "recover" in NrCAM Ϫ/Ϫ mice (Harley et al, 2018) and a similar kind of recovery in the Sema5b Ϫ/Ϫ mice may lead to limited changes in adult hearing thresholds. Our hearing assessment was underpowered to detect very subtle differences in hearing thresholds or wave I amplitude, and it is possible that slight differences may be detected with a larger cohort of mice in which males and females are analyzed separately (Milon et al, 2018).…”

Section: Discussionmentioning

confidence: 83%

“…We next assessed general patterns of cochlear innervation in Sema5b Ϫ/Ϫ and littermate control cochleae using anti-NF200 antibodies, which preferentially label SGNs (Harley et al, 2018) and anti-GAP43 antibodies, which preferentially label efferent fibers (Simmons et al, 1996). Previously, we showed high-magnification micrographs demonstrating that NF200 and GAP43 antibodies clearly delineate these different classes of fibers in the early postnatal cochlea (Harley et al, 2018). As shown in Figure 4, H and I, the SGN radial bundles and fibers contacting the IHCs (type I SGNs) were similar in the Sema5b Ϫ/Ϫ and control cochleae.…”

Section: Sema5b Is Required For Normal Sgn Branchingmentioning

confidence: 99%

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Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement during Development

et al. 2019

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During nervous system development, axons often undergo elaborate changes in branching patterns before circuits have achieved their mature patterns of innervation. In the auditory system, type I spiral ganglion neurons (SGNs) project their peripheral axons into the cochlear epithelium and then undergo a process of branch refinement before forming synapses with sensory hair cells. Here, we report that Semaphorin-5B (Sema5B) acts as an important mediator of this process. During cochlear development in mouse, immature hair cells express Sema5B, whereas the SGNs express both PlexinA1 and PlexinA3, which are known Sema5B receptors. In these studies, genetic sparse labeling and three-dimensional reconstruction techniques were leveraged to determine the morphologies of individual type I SGNs after manipulations of Sema5B signaling. Treating cultured mouse cochleae with Sema5B-Fc (to activate Plexin-As) led to type I SGNs with less numerous, but longer terminal branches. Conversely, cochleae from Sema5b knockout mice showed type I SGNs with more numerous, but shorter terminal branches. In addition, conditional loss of Plxna1 in SGNs (using Bhlhb5 Cre) led to increased type I SGN branching, suggesting that PlexinA1 normally responds to Sema5B in this process. In these studies, mice of either sex were used. The data presented here suggest that Sema5B-PlexinA1 signaling limits SGN terminal branch numbers without causing axonal repulsion, which is a role that distinguishes Sema5B from other Semaphorins in cochlear development.

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Section: Discussionmentioning

confidence: 83%

Section: Sema5b Is Required For Normal Sgn Branchingmentioning

confidence: 99%

Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement during Development

et al. 2019

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“…10, Supplementary Data 11). This list contained genes that were known to be expressed in LPsCs, including Prox1, Bmp2, Ngfr, and Nrcam 39,40,42,43 , and additional markers, including Tgfβr1, Fzd9 (Frizzled9), Elmo1, and Lsamp ( Fig. 5a, Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Characterization of the development of the mouse cochlear epithelium at the single cell level

et al. 2020

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Mammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points. Here we report on the analysis of those cells including the identification of both known and unknown cell types. Trajectory analysis for OHCs indicates four phases of gene expression while fate mapping of progenitor cells suggests that OHCs and their surrounding supporting cells arise from a distinct (lateral) progenitor pool. Tgfβr1 is identified as being expressed in lateral progenitor cells and a Tgfβr1 antagonist inhibits OHC development. These results provide insights regarding cochlear development and demonstrate the potential value and application of this data set.

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“…pruning (Harley et al, 2018). RNA sequencing data failed to detect NrCAM transcripts in the chicken BP at E6 (Munnamalai et al, 2017), although this time point precedes synapse formation in this organ.…”

Section: Semaphorin Signaling Genes In the Hcs Suggest A Role In Symentioning

confidence: 89%

“…Based on the timing of the expression we observe, Sema3D, Sema3F , and PlxnA1 may be involved in synapse formation in the BP. Neuronal cell adhesion molecule (NrCAM) has been shown to associate with Nrp2 (Julien et al, ) and recent work in the mouse inner ear has shown that it is involved in limiting ribbon synapses in the HCs, likely through inhibiting synapse formation or promoting pruning (Harley et al, ). RNA sequencing data failed to detect NrCAM transcripts in the chicken BP at E6 (Munnamalai et al, ), although this time point precedes synapse formation in this organ.…”

Section: Discussionmentioning

confidence: 99%

Expression of class III Semaphorins and their receptors in the developing chicken (Gallus gallus) inner ear

Scott¹,

Jia²,

Biesemeier³

et al. 2019

J of Comparative Neurology

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Class III Semaphorin (Sema) secreted ligands are known to repel neurites expressing Neuropilin (Nrp) and/or Plexin (Plxn) receptors. There is, however, a growing body of literature supporting that Sema signaling also has alternative roles in development such as synaptogenesis, boundary formation, and vasculogenesis. To evaluate these options during inner ear development, we used in situ hybridization or immunohistochemistry to map the expression of Sema3D, Sema3F, Nrp1, Nrp2, and PlxnA1 in the chicken (Gallus gallus) inner ear from embryonic day (E)5–E10. The resulting expression patterns in either the otic epithelium or its surrounding mesenchyme suggest that Sema signaling could be involved in each of the varied functions reported for other tissues. Sema3D expression flanking the sensory tissue in vestibular organs suggests that it may repel Nrp2‐ and PlxnA1‐expressing neurites of the vestibular ganglion away from nonsensory epithelia, thus channeling them into the sensory domains at E5–E8. Expression of Sema signaling genes in the sensory hair cells of both the auditory and vestibular organs on E8–E10 may implicate Sema signaling in synaptogenesis. In the nonsensory regions of the cochlea, Sema3D in the future tegmentum vasculosum opposes Nrp1 and PlxnA1 in the future cuboidal cells; the abutment of ligand and receptors in adjacent domains may enforce or maintain the boundary between them. In the mesenchyme, Nrp1 colocalized with capillary‐rich tissue. Sema3D immediately flanks this Nrp1‐expressing tissue, suggesting a role in endothelial cell migration towards the inner ear. In summary, Sema signaling may play multiple roles in the developing inner ear.

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Neuronal cell adhesion molecule (NrCAM) is expressed by sensory cells in the cochlea and is necessary for proper cochlear innervation and sensory domain patterning during development

Cited by 15 publications

References 75 publications

Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement during Development

Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement during Development

Characterization of the development of the mouse cochlear epithelium at the single cell level

Expression of class III Semaphorins and their receptors in the developing chicken (Gallus gallus) inner ear

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