GFRalpha3 is expressed predominantly in nociceptive sensory neurons

Orozco, Olivia; Walus, Lee; Sah, Dinah W.Y.; Pepinsky, R. Blake; Sanicola, Michele

doi:10.1046/j.0953-816x.2001.01596.x

Cited by 132 publications

(147 citation statements)

References 26 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…Based on immunohistochemical staining, GFRα3 is expressed largely on unmyelinated neurons. Variable expression on myelinated neurons, ranging from 0 to 14% of the total number of myelinated neurons in the DRG, has been reported (9,12,13). Behavioral recovery attributed to regeneration of unmyelinated axons is more robust than that by myelinated axons, consistent with a larger fraction of unmyelinated neurons expressing GFRα3 (9).…”

Section: Discussionsupporting

confidence: 52%

“…Because unmyelinated axons lack NgR expression, they might be less responsive to a blockade of myelin-associated inhibition than myelinated axons (11). In contrast, CGRP expression recovers following ART treatment, consistent with expression of the specific ART receptor, GFRα3, on unmyelinated neurons (9,12,13), suggesting that these afferents are regenerating (Fig. 3E).…”

Section: Resultsmentioning

confidence: 65%

See 1 more Smart Citation

Topographically specific regeneration of sensory axons in the spinal cord

Harvey

Gong

Rossomando

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Artemin, a member of the glial-derived neurotrophic factor family, promotes robust regeneration of sensory axons after dorsal root crush. We report here that several classes of sensory axons regenerate to topographically appropriate regions of the dorsal horn with artemin treatment. Projections of regenerated muscle and cutaneous myelinated sensory afferents are restricted to the correct spinal segments and to appropriate regions within spinal gray matter. Regenerated unmyelinated axons expressing calcitonin gene-related peptide project only to superficial laminae of the dorsal horn, where uninjured nociceptive afferents project normally. In contrast, intraventricular infusion of a soluble form of the Nogo receptor that blocks the action of several myelin-associated inhibitory proteins promotes relatively unrestricted regeneration of sensory axons throughout the dorsal white and gray matter of the spinal cord. These results demonstrate that cues capable of guiding regenerating axons to appropriate spinal targets persist in the adult mammalian cord, but only some methods of stimulating regeneration allow the use of these cues by growing axons.artemin | central nervous system regeneration | dorsal root | soluble Nogo receptor peptide | specificity G rowth of damaged axons in the adult spinal cord is inhibited by the presence of myelin-associated proteins, up-regulation of proteoglycan expression, and the absence of appropriate growth factors. Several agents that can partially overcome this inhibition permit some regeneration of spinal axons in contusion or transaction models of spinal cord injury (SCI) (1-4); however, the limited regeneration and difficulty in labeling specific subclasses of axons with known projection patterns within the spinal cord have impeded progress in determining whether these regenerated projections are specific.The regeneration of sensory axons into the spinal cord after dorsal root (DR) crush provides a useful preparation for assessing the precision with which regenerating axons project back to appropriate target areas within the central nervous system (CNS). Regrowth of damaged sensory axons within the spinal cord can be visualized by injecting neurotracers into peripheral nerves. Identification of individual classes of axons can be achieved by making injections close to target tissues where nerve branches contain single classes of sensory afferents. Because only the DRs are damaged, the architecture of the spinal cord is left intact, allowing clear identification of the central projections of regenerated axons.Without treatment, sensory axons regenerate only to the DR entry zone (DREZ), where they encounter inhibitory barriers within the CNS (5, 6). Application of two agents-a soluble Nogo receptor peptide (sNgR), which binds to Nogo receptor ligands and abrogates their inhibitory effect (7), and artemin (ART), a member of the glial-derived neurotrophic factor familypromote robust regeneration of sensory axons after DR crush (8, 9). The specificity of projections of specific classes of...

show abstract

Section: Discussionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 65%

Topographically specific regeneration of sensory axons in the spinal cord

Harvey

Gong

Rossomando

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…With this in mind, we examined trophic support in the aged ganglia by measuring the relative expression of receptors that bind the GDNF family of ligands, with particular interest in the GPI-anchored GFRα3 receptor. Neurons that express GFRα3, which binds the growth factor artemin, comprise approximately 20% of the lumbar mouse DRG population, show 99% colocalization with TRPV1 [31] and express the tyrosine kinase Ret [3]. Results show the relative abundance of GFRα3 is decreased in aged ganglia on both the transcriptional and translational level in lumbar DRG suggesting this TRPV1 enriched population is preferentially affected in aging systems.…”

Section: Discussionmentioning

confidence: 91%

“…1). With this possibility in mind, we examined expression of receptors for artemin, a neurotrophic factor that supports a nociceptor neuron population that expresses high levels of TRPV1 [31]. We examined the relative expression of the artemin specific GPI-linked binding component GFRα3 and its associated signaling component, the tyrosine kinase receptor Ret in lumbar DRG using RT-PCR and immunoblot assays (Table 1; Fig.…”

Section: The Reduction In Trpv1 May Results From Decreased Trophic Facmentioning

confidence: 99%

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Wang

Davis

Zwick³

et al. 2006

Neurobiology of Aging

View full text Add to dashboard Cite

Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene expression that correlate with reduced sensory perception. In this study we compared young and aged mice to identify proteins that might contribute to this loss of sensation. We first show using behavioral testing that thermal sensitivity in aged male and female mice is reduced. Expression of sodium channel (Nav1.8 and Nav1.9) and transient receptor potential vanilloid (TRPV) channels in DRG and peripheral nerves of young and old male mice was then examined. Immunoblotting and RT-PCR assays showed reduced Nav1.8 levels in aged mice. No change was measured in TRPV1 mRNA levels in DRG though TRPV1 protein appeared reduced in the DRG and peripheral nerves. The GFRα3 receptor, which binds the growth factor artemin and is expressed by TRPV1-positive neurons, was also decreased in the DRG of aged animals. These findings indicate that loss of thermal sensitivity in aging animals may result from a decreased level of TRPV1 and Nav1.8 and decreased trophic support that inhibits efficient transport of channel proteins to peripheral afferents.

show abstract

“…Artemin is an important regulator of the induction of neuronal proliferation and regeneration under physiologic conditions (Baloh et al, 2000;Enomoto et al, 2001;Honma et al, 2002) and GFRα3 is upregulated in the distal nerve segment after sciatic transsection (Orozco et al, 2001). On the other hand, mutations of the RET receptor cause several human diseases such as papillary thyroid carcinoma, multiple endocrine neoplasia (types 2A and 2B), and Hirschsprung's disease (Takahashi, 2001).…”

Section: Discussionmentioning

confidence: 99%