TMEM184B promotes pruriceptive neuron specification to facilitate itch sensitivity

Nociceptive and pruriceptive neurons in the dorsal root ganglia (DRG) convey sensations of pain and itch to the spinal cord, respectively. A sub-population of these neurons, marked by Somatostatin () expression, is responsible for sensing IL-31, a mediator of acute itch, atopic dermatitis, and asthma. Here we show that , a gene with known roles in axon degeneration and nerve terminal maintenance, is required for the expression of a large cohort of itch receptors such as those for IL-31, Leukotriene C4, and Histamine. Mice lacking fail to respond to IL-31, but maintain normal responses to pain and mechanical force, suggesting a specific defect in pruriception. Lineage-tracing studies using -driven Cre recombinase show a loss of pruriceptive neurons in -mutant mice, indicating a defect in neuron subtype specification. Accordingly, Wnt-dependent transcriptional signatures and signaling components, which are essential for neuronal subtype specification during development, are markedly reduced in -mutant embryonic DRG. Lentiviral re-expression of Tmem184b in mutant embryonic neurons restores Wnt signatures, whereas re-expression of Tmem184b in adult DRG fails to restore itch responses. Together, these data demonstrate that Tmem184b promotes adult somatosensation through developmental Wnt signaling and specification of pruriceptive neurons.