Differential gene expression in the rat after injury of dorsal root ganglion neurons in vivo, and simulation injury of Schwann cells and oligodendrocytes in vitro was analyzed using high‐density cDNA microarrays. The analyses were carried out to study the genetic basis of peripheral nerve regeneration, and to compare gene regulation in glia of the central (oligodendrocyte) and peripheral (Schwann cell) nervous systems. The genes showing significant differential regulation in the three study groups represented all aspects of cellular metabolism. However, two unexpected observations were made. Firstly, a number of identical genes were differentially regulated in activated Schwann cells, activated oligodendrocytes and regenerating DRG neurons. Specifically, a group of 113 out of 210 genes that were down‐regulated in Schwann cells upon lipopolysaccharide (LPS) treatment, were identical to genes up‐regulated in the injured, regenerating DRG. Furthermore, a group of 53 out of 71 genes that were down‐regulated in interferon gamma (IFN‐γ)/LPS‐activated oligodendrocytes, were identical to genes up‐regulated in the DRG neurons. Finally, 22 genes were common to these three groups, i.e., down‐regulated in activated oligodendrocytes, down‐regulated in activated Schwann cells, and up‐regulated in regenerating DRG neurons. Secondly, a group of 16 cell‐cycle and proliferation‐related genes were up‐regulated in the DRG following sciatic nerve crush, despite the absence of cells undergoing mitosis in the DRG, or any significant presence of apoptosis‐related gene expression. Therefore, it appears that in these three cell types, large sets of genes are reciprocally regulated upon injury and/or activation. This suggests that the activation of the injury‐related gene expression program in cell derivatives of the neuroectoderm involves, in part, highly conserved genetic elements. J. Cell. Biochem. 88: 970–985, 2003. © 2003 Wiley‐Liss, Inc.

Gene expression monitoring using gene expression microarrays represents an extremely powerful technology for gene discovery in a variety of systems. We describe the results of seven experiments using Incyte GEM technology to compile a proprietary portfolio of data concerning differential gene expression in six different models of neuronal differentiation and regeneration, and recovery from injury or disease. Our first two experiments cataloged genes significantly up- or down-regulated during two phases of the retinoic acid-induced differentiation of the embryonal carcinoma line Ntera-2. To identify genes involved in neuronal regeneration we performed three GEM experiments, which included changes in gene expression in rat dorsal root ganglia during the healing of experimentally injured sciatic nerve, in regenerating neonatal opossum spinal cord, and during lipopolysaccharide stimulation of primary cultures of rat Schwann cells. Finally we have monitored genes involved in the recovery phase of the inflammatory disease of the rat spinal cord, experimental allergic encephalomyelitis, as well as those responsible for protection from oxidative stress in a glutamate-resistant rat hippocampal cell line. Analysis of the results of the approximately 70,000 data points collected is presented.