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Different requirements for GFR?2-signaling in three populations of cutaneous sensory neurons.

ABSTRACT: Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFR?'s, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFR?2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFR?2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large A?-LTMRs. Using GFR?2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFR?2 controls the cell size but not the survival of both C-LTMRs and A?-LTMRs. In contrast to the nonpeptidergic neurons, GFR?2 is not required for the target innervation of C-LTMRs and A?-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFR?2 immunoreactivity in mature animals suggests that these neurons switch their GFR? signaling pathways during postnatal development.

SUBMITTER: Kupari J

PROVIDER: S-EPMC4128720 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

Kupari Jussi J Airaksinen Matti S MS

PloS one 20140811 8

Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of g ...[more]

PMID: 25111710

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Project description:The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1-dependent responses to both innocuous and noxious mechanical force. Mechanically evoked action potentials in cutaneous myelinated A-fiber and unmyelinated C-fiber neurons were quantified using the ex vivo skin-nerve preparation to record from the saphenous nerve, which terminates in the dorsal hairy skin of the hindpaw. Our data reveal that in TRPC1-deficient mice, mechanically evoked action potentials were decreased by nearly 50% in slowly adapting A?-fibers, which largely innervate Merkel cells, and in rapidly adapting A?-Down-hair afferent fibers compared with wild-type controls. In contrast, differences were not found in slowly adapting A?-mechanoreceptors or unmyelinated C-fibers, which primarily respond to nociceptive stimuli. These results suggest that TRPC1 may be important in the detection of innocuous mechanical force. We concurrently investigated the role of TRPC1 in behavioral responses to mechanical force to the plantar hindpaw skin. For innocuous stimuli, we developed a novel light stroke assay using a "puffed out" cotton swab. Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior.

Dataset Information

Different requirements for GFR?2-signaling in three populations of cutaneous sensory neurons.

Publications

Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

Similar Datasets

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