Prdm12 is required for survival and maturation of developing nocicepotive neurons

Dorsal root ganglia contain pain-related nociceptive sensory neurons arising in two successive, Ngn1 and Ngn2 dependant neurogenic waves. Nociceptive progenitors are initially dependent on the expression of the neurotrophic receptor TrkA for their survival, development and maturation. Here, we show that the transcriptional regulator Prdm12, whose mutation causes congenital insensitivity to pain in human, is selectively expressed in the developing nociceptors arising from both neurogenic waves. We generated a Prdm12 knockout mouse line to define its function and found that Prdm12 is required for the initiation of the expression of TrkA and therefore for the survival of nociceptive progenitors. Gain of function experiments in Xenopus indicates that Prdm12 cooperates with Ngn1 and Ngn2 to promote in sensory progenitors a nociceptive fate. Late excision of Prdm12 in developing postmitotic progenitors also affects their development, and leads to a downregulation of TrkA and of other nociceptive markers, including the transcription factor Runx1. Together, these results establish Prdm12 as a master regulator of nociceptive neurons, acting at different steps of their development.