Conserved Transcriptional Architecture of Pain (#133)
After nerve injury, pain sensing neurons drastically alter their transcriptional profile and this response leads to chronic pain via a completely unknown mechanism. Moreover, from exome sequencing of families with congenital insensitivity to pain, multiple transcriptional regulators of pain perception have been identified. To map the transcriptional networks that govern pain perception, we screened all conserved transcription factors for a role in basic neuronal development and pain perception. Using Class IV sensory neuron-specific RNAi knockdown in Drosophila, we found ~50 novel conserved transcriptional regulators governing sensory neuron development and function. To identify factors specifically regulating nociceptor development, we evaluated sensory neuron dendritic pattern formation for all new pain transcription factors identified. For developmental regulators of nociceptors, phenotypes ranged from control of cell fate determination, dendrite branching, lateral extension, dendritic arborisation and routing. We are now mapping the transcriptional hierarchy of this network in the fly, and investigating select pain transcription factors for a role in nociceptor development or function in KO mice and human ES cells