The transcriptional landscape of dorsal root ganglia after sciatic nerve transection

Although adult mammalian peripheral nerves have an intrinsic ability to spontaneously regenerate after transection, the functional outcomes of peripheral nerve repair are often unsatisfactory even with the help of currently available therapies1,2,3. Neuroscientists and clinicians have been striving to gain more detailed insights into molecular mechanisms underlying peripheral nerve regeneration and to develop more effective therapeutic approaches to peripheral nerve injury. Following axonal transection, a series of pathophysiological events occurs in the lesioned tissues, and highly orchestrated gene expression programs are activated, accompanied by phenotypic and functional changes of neural and non-neural cells4. Previous studies have examined time-dependent expression changes of many genes in proximal and distal peripheral nerves after nerve injury by using cDNA array-based expression analysis that allows the identification of a diverse spectrum of genes that are differentially expressed between normal and disease conditions4,5,6,7,8,9. Despite high-throughput gene data obtained in these studies, more comprehensive analysis remains to be done by the aid of newly-developed statistical and bioinformatic tools for acquiring valuable information about molecular regulation of transcriptional responses of the peripheral nervous system to traumatic injury. Sciatic nerve injury is a commonly used model for peripheral nerve regeneration studies, and sensory neurons extending into the sciatic nerve are located in the L4–L6 dorsal root ganglia (DRGs). Once primary sensory neurons are primed by peripheral axonal injury, they are likely to grow more rapidly in response to a subsequent lesion, which has been known as the conditioning effect10,11. Peripheral axonal injury triggers axonal growth from DRG neurons, conditions neurons to grow extensively, and facilitates peripheral nerve regeneration12. Several molecular mediators in DRGs have been identified to play regulatory roles in peripheral nerve regeneration13,14,15,16,17,18,19,20, but more comprehensive studies are still required to obtain a global perspective of how these molecular mediators, coupled with the related bioprocesses and signaling pathways, are deliberately orchestrated to activate the intrinsic regenerative programs of peripheral nerves. The aim of this study was to investigate the transcriptional landscape of rat DRGs in response to sciatic nerve transection. The cDNA microarray analysis showed that thousands of genes were differentially expressed at different time points following sciatic nerve transection. Various bioinformatic tools were subsequently used to analyze the microarray-derived data sets, revealing some interesting aspects about gene regulation of peripheral nerve regeneration.