ArticlePLoS genetics2017
Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Audiovestibular Dysfunction Related to Long COVID-19 Syndrome: A Systematic Review of Characteristics, Pathophysiology, Diagnosis, and Management.International journal of molecular sciences · 2026Pooled it
- Article
- Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- EPHRIN-A1 and -A2 act as positive growth factors for developing spiral ganglion radial bundles.Developmental biology · 2025Article
- Chromatin remodeling protein CHD4 regulates axon guidance of spiral ganglion neurons in the developing cochlea.bioRxiv : the preprint server for biology · 2025Article
- Targeted spiral ganglion neuron degeneration in parvalbumin-Cre neonatal mice.Molecular therapy. Methods & clinical development · 2025Article
- Trophic and temporal dynamics of macrophage biology in human inner ear organogenesis.Frontiers in immunology · 2025Article
- Functional pathogenicity of ESRRB variant of uncertain significance contributes to hearing loss (DFNB35).Scientific reports · 2024Article
- Early Steps towards Hearing: Placodes and Sensory Development.International journal of molecular sciences · 2023Review
- Cochlear hair cell innervation is dependent on a modulatory function of Semaphorin-3A.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Hearing loss and tinnitus: association studies for complex-hearing disorders in mouse and man.Human genetics · 2022Review
- Article
- Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies.Genes · 2021Article
- The role of Neuropilin-1 in COVID-19.PLoS pathogens · 2021Review
- Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement during Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Expression of class III Semaphorins and their receptors in the developing chicken (Gallus gallus) inner ear.The Journal of comparative neurology · 2019Article
- Fibroblast growth factor 12 is expressed in spiral and vestibular ganglia and necessary for auditory and equilibrium function.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.