PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis

Luca Bartesaghi, Yiqiao Wang, Paula Fontanet, Simone Wanderoy, Finja Berger, Haohao Wu, Natalia Akkuratova, Filipa Bouçanova, Jean Jacques Médard, Charles Petitpré, Mark A. Landy, Ming Dong Zhang, Philip Harrer, Claudia Stendel, Rolf Stucka, Marina Dusl, Maria Eleni Kastriti, Laura Croci, Helen C. Lai, Gian Giacomo ConsalezAlexandre Pattyn, Patrik Ernfors, Jan Senderek, Igor Adameyko, Francois Lallemend, Saida Hadjab, Roman Chrast

Research output: Contribution to journalArticle

Abstract

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. The sensation of pain, temperature, and itch by neurons of the nociceptive lineage is essential for animal survival. Bartesaghi et al. report that the transcriptional regulator PRDM12 is indispensable in neural crest cells (NCCs) for the initiation of the sensory neuronal differentiation program that generates the entire nociceptive lineage.

Original languageEnglish
Pages (from-to)3484-3492.e4
JournalCell Reports
Volume26
Issue number13
DOIs
Publication statusPublished - Mar 26 2019

Keywords

  • neural crest cells
  • neurogenesis
  • nociceptive neurons
  • pain
  • Prdm12

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Bartesaghi, L., Wang, Y., Fontanet, P., Wanderoy, S., Berger, F., Wu, H., Akkuratova, N., Bouçanova, F., Médard, J. J., Petitpré, C., Landy, M. A., Zhang, M. D., Harrer, P., Stendel, C., Stucka, R., Dusl, M., Kastriti, M. E., Croci, L., Lai, H. C., ... Chrast, R. (2019). PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis. Cell Reports, 26(13), 3484-3492.e4. https://doi.org/10.1016/j.celrep.2019.02.098