Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea.

Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea.

Salehi Pezhman; Ge Marshall X; Gundimeda Usha; Michelle Baum Leah; Lael Cantu Homero; Lavinsky Joel; Tao Litao; Myint Anthony; Cruz Charlene; Wang Juemei; Nikolakopoulou Angeliki Maria; Abdala Carolina; Kelley Matthew William; Ohyama Takahiro; Coate Thomas Matthew; Friedman Rick A

PLoS genetics

2017

2017-10

Neuropilin-1 (Nrp1) encodes the transmembrane cellular receptor neuropilin-1, which is associated with cardiovascular and neuronal development and was within the peak SNP interval on chromosome 8 in our prior GWAS study on age-related hearing loss (ARHL) in mice. In this study, we generated and characterized an inner ear-specific Nrp1 conditional knockout (CKO) mouse line because Nrp1 constitutive knockouts are embryonic lethal. In situ hybridization demonstrated weak Nrp1 mRNA expression late in embryonic cochlear development, but increased expression in early postnatal stages when cochlear hair cell innervation patterns have been shown to mature. At postnatal day 5, Nrp1 CKO mice showed disorganized outer spiral bundles and enlarged microvessels of the stria vascularis (SV) but normal spiral ganglion cell (SGN) density and presynaptic ribbon body counts; however, we observed enlarged SV microvessels, reduced SGN density, and a reduction of presynaptic ribbons in the outer hair cell region of 4-month-old Nrp1 CKO mice. In addition, we demonstrated elevated hearing thresholds of the

Female; Male; Animals; Mice; Neurogenesis; Neurons/cytology; Neuropilin-1/genetics/*metabolism; Semaphorin-3A/genetics/*metabolism; Signal Transduction; Spiral Ganglion/cytology/*embryology; Inbred C57BL; Knockout

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e1007048–e1007048

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