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EMBO Rep. 2016 Apr;17(4):585-600. doi: 10.15252/embr.201540983. Epub 2016 Feb 29.

A subpopulation of itch-sensing neurons marked by Ret and somatostatin expression.

Author information

1
EMBL Mouse Biology Unit, Monterotondo, Italy.
2
EMBL Mouse Biology Unit, Monterotondo, Italy Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.
3
IRCCS Santa Lucia, Rome, Italy.
4
EMBL Mouse Biology Unit, Monterotondo, Italy Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany paul.heppenstall@embl.it.

Abstract

Itch, the unpleasant sensation that elicits a desire to scratch, is mediated by specific subtypes of cutaneous sensory neuron. Here, we identify a subpopulation of itch-sensing neurons based on their expression of the receptor tyrosine kinase Ret. We apply flow cytometry to isolate Ret-positive neurons from dorsal root ganglia and detected a distinct population marked by low levels of Ret and absence of isolectin B4 binding. We determine the transcriptional profile of these neurons and demonstrate that they express neuropeptides such as somatostatin (Sst), the NGF receptor TrkA, and multiple transcripts associated with itch. We validate the selective expression of Sst using an Sst-Cre driver line and ablated these neurons by generating mice in which the diphtheria toxin receptor is conditionally expressed from the sensory neuron-specific Avil locus. Sst-Cre::Avil(iDTR) mice display normal nociceptive responses to thermal and mechanical stimuli. However, scratching behavior evoked by interleukin-31 (IL-31) or agonist at the 5HT1F receptor is significantly reduced. Our data provide a molecular signature for a subpopulation of neurons activated by multiple pruritogens.

KEYWORDS:

5HT1F; DRG; IL‐31; sensory neurons

PMID:
26929027
PMCID:
PMC4818769
DOI:
10.15252/embr.201540983
[Indexed for MEDLINE]
Free PMC Article

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