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Papers of the Week

Papers: 23 Mar 2019 - 29 Mar 2019

Animal Studies

2019 Mar 26

Cell Rep



Editor's Pick

Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA.


Desiderio S, Vermeiren S, Van Campenhout C, Kricha S, Malki E, Richts S, Fletcher EV, Vanwelden T, Schmidt BZ, Henningfeld KA, Pieler T, Woods GC, Nagy V, Verfaillie C, Bellefroid EJ
Cell Rep. 2019 Mar 26; 26(13):3522-3536.e5.
PMID: 30917309.


In humans, many cases of congenital insensitivity to pain (CIP) are caused by mutations of components of the NGF/TrkA signaling pathway, which is required for survival and specification of nociceptors and plays a major role in pain processing. Mutations in PRDM12 have been identified in CIP patients that indicate a putative role for this transcriptional regulator in pain sensing. Here, we show that Prdm12 expression is restricted to developing and adult nociceptors and that its genetic ablation compromises their viability and maturation. Mechanistically, we find that Prdm12 is required for the initiation and maintenance of the expression of TrkA by acting as a modulator of Neurogenin1/2 transcription factor activity, in frogs, mice, and humans. Altogether, our results identify Prdm12 as an evolutionarily conserved key regulator of nociceptor specification and as an actionable target for new pain therapeutics.