TMEM184B controls pruriceptor specification and function [article]

Erik G. Larsen, Tiffany S. Cho, Matthew L. McBride, Jing Feng, Bhagyashree Manivannan, Cynthia Madura, Nathaniel E. Klein, Elizabeth B. Wright, Hector D. Garcia-Verdugo, Chelsea Jarvis, Rajesh Khanna, Hongzhen Hu (+2 others)
2020 bioRxiv   pre-print
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 (Sst) expression, is responsible for detecting the cytokine IL-31, a mediator of acute itch and atopic dermatitis. The mechanisms responsible for specifying this population are largely unknown. Here we show that Tmem184b, a gene with known roles in axon degeneration and nerve terminal maintenance, is
more » ... equired for the expression of a substantial cohort of receptors, including IL31RA, that mediate acute itch. Mice lacking Tmem184b fail to respond to IL-31, but maintain normal responses to pain and mechanical force, suggesting a specific defect in pruriception. The number of Sst+ neurons is reduced in Tmem184b-mutant mice, indicating a likely defect in neuron subtype specification. Rescue experiments in adults versus embryonic neurons support a primary role for TMEM184B during development. We evaluated DRG gene expression across embryonic and early postnatal development and found that levels of Wnt signaling components are significantly reduced in embryonic DRG from Tmem184b-mutants and restored upon re-expression of Tmem184b. In summary, we have identified a mechanism controlled by TMEM184B that gates proper specification of pruriceptive neurons in the DRG through control of Wnt signaling. TMEM184B is thus critical for proper pruriceptive development and adult somatosensation.
doi:10.1101/2020.01.25.919902 fatcat:shdupcixmnbh5pqxikkv3ihikm