title: A subpopulation of itch-sensing neurons marked by Ret and somatostatin expression.
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.
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Kalina K
authors.initials: KK
authors.lastname: Stantcheva
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.
authors.forename: Loredana
authors.initials: L
authors.lastname: Iovino
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Rahul
authors.initials: R
authors.lastname: Dhandapani
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Concepcion
authors.initials: C
authors.lastname: Martinez
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Castaldi
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Nocchi
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Emerald
authors.initials: E
authors.lastname: Perlas
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Portulano
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Pesaresi
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Kalyanee S
authors.initials: KS
authors.lastname: Shirlekar
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: de Castro Reis
authors.affiliation: IRCCS Santa Lucia, Rome, Italy.
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Paparountas
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bilbao
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany paul.heppenstall@embl.it.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D020869:Gene Expression Profiling; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics; D017403:In Situ Hybridization; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics; D009475:Neurons, Afferent / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011537:Pruritus / Q000235:genetics*; D020800:Receptor, Nerve Growth Factor / Q000235:genetics; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics*
chemical_list: C113762:Avil protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D037102:Lectins; D008840:Microfilament Proteins; D009479:Neuropeptides; D020800:Receptor, Nerve Growth Factor; D013004:Somatostatin; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse
keywords: 5HT1F; DRG; IL‐31; sensory neurons