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Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea
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نویسنده
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salehi p. ,ge m.x. ,gundimeda u. ,michelle baum l. ,lael cantu h. ,lavinsky j. ,tao l. ,myint a. ,cruz c. ,wang j. ,nikolakopoulou a.m. ,abdala c. ,kelley m.w. ,ohyama t. ,coate t.m. ,friedman r.a.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 10
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چکیده
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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 2-month-old and 4-month-old nrp1 cko mice at frequencies ranging from 4 to 32khz when compared to 2-month-old mice. these data suggest that conditional loss of nrp1 in the inner ear leads to progressive hearing loss in mice. we also demonstrated that mice with a truncated variant of nrp1 show cochlear axon guidance defects and that exogenous semaphorin-3a,a known neuropilin-1 receptor agonist,repels sgn axons in vitro. these data suggest that neuropilin-1/semaphorin-3a signaling may also serve a role in neuronal pathfinding in the developing cochlea. in summary,our results here support a model whereby neuropilin-1/semaphorin-3a signaling is critical for the functional and morphological integrity of the cochlea and that nrp1 may play a role in arhl. © 2017 salehi et al.
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آدرس
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usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca,united states,department of anatomy and neurobiology,northeast ohio medical university,rootstown,oh, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, department of medicine,temple university school of medicine,philadelphia,pa, United States, department of biology,georgetown university,washington,dc, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca,united states,graduate program in surgical sciences,federal university of rio grande do sul,porto alegre,rio grande do sul, Brazil, stem cell biology & regenerative medicine,keck school of medicine,university of southern california,los angeles,ca, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, department of physiology and biophysics,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, national institute on deafness and other communication disorders,bethesda,md, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca, United States, department of biology,georgetown university,washington,dc, United States, usc-tina and rick caruso department of otolaryngology-head & neck surgery,zilkha neurogenetic institute,usc keck school of medicine,university of southern california,los angeles,ca,united states,department of otolaryngology,zilkha neurogenetic institute,keck school of medicine,university of southern california,los angeles,ca, United States
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Authors
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