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

Simon Desiderio | Zendy; Simon Vermeiren | Zendy; Claude Van Campenhout | Zendy; Sadia Kricha | Zendy; Elisa Malki | Zendy; Sven Richts | Zendy; Emily V. Fletcher | Zendy; Thomas Vanwelden | Zendy; Béla Z. Schmidt | Zendy; Kristine A. Henningfeld | Zendy; Tomas Pieler | Zendy; C. Geoffrey Woods | Zendy; Vanja Nagy | Zendy; Catherine M. Verfaillie | Zendy; Eric Bellefroid | Zendy

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

Author(s) -

Simon Desiderio,

Simon Vermeiren,

Claude Van Campenhout,

Sadia Kricha,

Elisa Malki,

Sven Richts,

Emily V. Fletcher,

Thomas Vanwelden,

Béla Z. Schmidt,

Kristine A. Henningfeld,

Tomas Pieler,

C. Geoffrey Woods,

Vanja Nagy,

Catherine M. Verfaillie,

Eric Bellefroid

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.02.097

Subject(s) - tropomyosin receptor kinase a , nociceptor , regulator , nociception , nerve growth factor , transcription factor , biology , neuroscience , microbiology and biotechnology , signal transduction , sensory system , sensory neuron , caenorhabditis elegans , receptor , genetics , gene

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.

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