The Regulatory Functionof The Transcription Factor Nfic During Nociceptor Development

Pain, a prominent symptom of many clinical conditions, could originate from cutaneous, muscle, or visceral organs. Currently much of the knowledge about the mechanisms of pain derives from experimental studies of somatic nociception, though deep tissue pain has much greater clinical relevence. Published data showed that non-peptidergic sensory neurons mainly innervate cutaneously, while deep tissue sensory neurons are peptidergic, suggesting that the neural mechanisms of pain revealed by studies on superficial structure may not apply equally to deep tissue. The development of specific and efficient visceral pain therapies requires better understanding of the regulatory mechanisms underlying peptidergic neuron development. Previous studies revealed a master role of transcription factor Runx1 in the specification of non-peptidergic sensory neurons: in Runx1 knock-out mice, most of presumptive non-peptidergic neurons express peptidergic marker CGRP and thus adapt peptidergic cell fate. Genome-scale microarray analysis of Runx1loss-of-function DRG reveals transcription factor Nfic as a candidate to regulate CGRP expression. In this project, the expression pattern of Nfic in DRG was analyzed,and the regulatory function of Nifc on CGRP expression was revealed by microarray and in situ analysis of Nfic knock-out DRG. Furthermore, the expression of a series of Nfic down-stream target candidates, including Mrg subfamily of G protein-coupled receptors, were tested by in situ hybridization. The results showed that Nfic could play an important role in the specification of C-mechanoreceptors.