Developmental changes of gene expression after spinal cord injury in neonatal opossums

Changes in gene expression have been measured 24 h after injury to mammalian spinal cords that can and cannot regenerate. In opossums there is a critical period of development when regeneration stops being possible: at 9 days postnatal cervical spinal cords regenerate, at 12 days they do not. By the use of marsupial cDNA microarrays, we detected 158 genes that respond differentially to injury at the two ages critical for regeneration. For selected candidates additional measurements were made by real-time PCR and sites of their expression were shown by immunostaining. Candidate genes have been classified so as to select those that promote or prevent regeneration. Up-regulated by injury at 8 days and/or down-regulated by injury at 13 days were genes known to promote growth, such as Mitogen-activated protein kinase kinase 1 or transcription factor TCF7L2. By contrast, at 13 days, up-regulation occurred of inhibitory molecules, including annexins, ephrins, and genes related to apoptosis and neurodegenerative diseases. Certain genes such as calmodulin 1 and NOGO, changed expression similarly in animals that could and could not regenerate without any additional changes in response to injury. These findings confirmed and extended changes of gene expression found in earlier screens on 9 and 12 day preparations without lesions and provide a comprehensive list of genes that serve as a basis for testing how identified molecules, singly or in combination, promote and prevent central nervous system regeneration.

Research Highlights
► 158 genes respond differently in injured spinal cords that can and cannot regenerate.
► Identified genes are classified as candidates to promote or prevent regeneration.
► NOGO changed expression similarly in animals that could and could not regenerate.
► Up-regulated by injury in animals that can regenerate is the transcription factor TCF7L2.
► Up-regulated in animals that cannot regenerate are neurodegeneration-related genes.