ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
RET signaling is required for survival and normal function of nonpeptidergic nociceptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 84 citations in OpenAlex.
- Comprehensive mapping of sensory and sympathetic innervation of the developing kidney.Cell reports · 2024Article
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- Comprehensive mapping of sensory and sympathetic innervation of the developing kidney.bioRxiv : the preprint server for biology · 2024Article
- c-Kit Receptor Maintains Sensory Axon Innervation of the Skin through Src Family Kinases.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Proteomic and clinical biomarkers for acute mountain sickness in a longitudinal cohort.Communications biology · 2022Article
- Selective disruption of trigeminal sensory neurogenesis and differentiation in a mouse model of 22q11.2 deletion syndrome.Disease models & mechanisms · 2022Article
- Distribution of acid-sensing ion channel subunits in human sensory neurons contrasts with that in rodents.Brain communications · 2022Article
- Genetic interplay between transcription factor Pou4f1/Brn3a and neurotrophin receptor Ret in retinal ganglion cell type specification.Neural development · 2021Article
- Spatiotemporal mapping of sensory and motor innervation of the embryonic and postnatal mouse urinary bladder.Developmental biology · 2021Article
- Effects of Venlafaxine, Risperidone and Febuxostat on Cuprizone-Induced Demyelination, Behavioral Deficits and Oxidative Stress.International journal of molecular sciences · 2021Article
- The development of somatosensory neurons: Insights into pain and itch.Current topics in developmental biology · 2021Review
- Cross Talk of BDNF and GDNF in Spinal Substantia Gelatinosa (Lamina II): Focus on Circuitry.Advances in experimental medicine and biology · 2021Article
- Interplay of BDNF and GDNF in the Mature Spinal Somatosensory System and Its Potential Therapeutic Relevance.Current neuropharmacology · 2021Review
- Glial cell line-derived neurotrophic factors (GFLs) and small molecules targeting RET receptor for the treatment of pain and Parkinson's disease.Cell and tissue research · 2020Review
- Myelinating Schwann cells ensheath multiple axons in the absence of E3 ligase component Fbxw7.Nature communications · 2019Article
- Ret Signaling Is Required for Tooth Pulp Innervation during Organogenesis.Journal of dental research · 2019Article
- Natural Selection Equally Supports the Human Tendencies in Subordination and Domination: A Genome-Wide Study WithFrontiers in genetics · 2019Article
- Human vs. Mouse Nociceptors - Similarities and Differences.Neuroscience · 2018Article
- Temporally restricted death and the role of p75NTR as a survival receptor in the developing sensory nervous system.Developmental neurobiology · 2018Article
- Characterization of retinal ganglion cell, horizontal cell, and amacrine cell types expressing the neurotrophic receptor tyrosine kinase Ret.The Journal of comparative neurology · 2018Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Small unmyelinated sensory neurons classified as nociceptors are divided into two subpopulations based on phenotypic differences, including expression of neurotrophic factor receptors. Approximately half of unmyelinated nociceptors express the NGF receptor TrkA, and half express the GDNF family ligand (GFL) receptor Ret. The function of NGF/TrkA signaling in the TrkA population of nociceptors has been extensively studied, and NGF/TrkA signaling is a well established mediator of pain. The GFLs are analgesic in models of neuropathic pain emphasizing the importance of understanding the physiological function of GFL/Ret signaling in nociceptors. However, perinatal lethality of Ret-null mice has precluded the study of the physiological role of GFL/Ret signaling in the survival, maintenance, and function of nociceptors in viable mice. We deleted Ret exclusively in nociceptors by crossing nociceptor-specific Na(v)1.8 Cre and Ret conditional mice to produce Ret-Na(v)1.8 conditional knock-out (CKO) mice. Loss of Ret exclusively in nociceptors results in a reduction in nociceptor number and size, indicating that Ret signaling is important for the survival and trophic support of these cells. Ret-Na(v)1.8 CKO mice exhibit reduced epidermal innervation but normal central projections. In addition, Ret-Na(v)1.8 CKO mice have increased sensitivity to cold and increased formalin-induced pain, demonstrating that Ret signaling modulates the function of nociceptors in vivo. Enhanced inflammation-induced pain may be mediated by decreased prostatic acid phosphatase (PAP), as PAP levels are markedly reduced in Ret-Na(v)1.8 CKO mice. The results of this study identify the physiological role of endogenous Ret signaling in the survival and function of nociceptors.
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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 OpenQuestion graph.