Cell Reports
Volume 26, Issue 13, 26 March 2019, Pages 3484-3492.e4
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Report
PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis

https://doi.org/10.1016/j.celrep.2019.02.098Get rights and content
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Highlights

  • PRDM12 is expressed in neural crest cells (NCCs) and all nociceptive lineage neurons

  • Inactivation of PRDM12 results in the absence of the entire nociceptive lineage

  • Forced expression of PRDM12 in NCCs represses non-nociceptor fates

  • PRDM12 regulates progenitor proliferation and the sensory neurogenesis program

Summary

The sensation of pain is essential for the preservation of the functional integrity of the body. However, the key molecular regulators necessary for the initiation of the development of pain-sensing neurons have remained largely unknown. Here, we report that, in mice, inactivation of the transcriptional regulator PRDM12, which is essential for pain perception in humans, results in a complete absence of the nociceptive lineage, while proprioceptive and touch-sensitive neurons remain. Mechanistically, our data reveal that PRDM12 is required for initiation of neurogenesis and activation of a cascade of downstream pro-neuronal transcription factors, including NEUROD1, BRN3A, and ISL1, in the nociceptive lineage while it represses alternative fates other than nociceptors in progenitor cells. Our results thus demonstrate that PRDM12 is necessary for the generation of the entire lineage of pain-initiating neurons.

Keywords

neurogenesis
pain
nociceptive neurons
Prdm12
neural crest cells

Cited by (0)

11

These authors contributed equally

12

These authors contributed equally

13

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