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

Summary The sensation of pain is essential for the preservation of the functional integrityof 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 regulatorPRDM12, which is essential for pain perception in humans, results in a complete absence of the nociceptivelineage, while proprioceptiveand touch-sensitive neurons remain. Mechanistically, our data reveal that PRDM12 is required for initiation of neurogenesisand activation of a cascade of downstream pro-neuronal transcription factors, including NEUROD1, BRN3A, and ISL1, in the nociceptivelineage while it represses alternative fates other than nociceptorsin progenitor cells. Our results thus demonstrate that PRDM12 is necessary for the generation of the entire lineage of pain-initiating neurons.