Understanding Nerve Regeneration
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Understanding of the cellular and molecular biology underlying nerve tissue development and regenerative capacity after injury is key to basic understanding of development, but also to developing the clinical knowledge necessary to reverse and repair injury to nerve tissue. Much is known about the process of nerve regeneration in fish and mammals. For example, when the optic nerve of a mouse is severed, the distal portion of axons leading from the retina into the brain die and do not regenerate, while in fish, the cut axons promptly sprout new shoots (neurites) which rapidly re-enervate the brain. REP funds helped support testing the hypothesis that injury to nerve tissue results in differential gene expression and/or temporal differences in gene activation/deactivation between fish and mammals. We (I and my students) used (1) DNA microarray analysis to determine changes in gene expression resulting from cutting the optic nerve in zebrafish; (2) confocal microscopy to visually track nerve regeneration following injury, and (3) quantitative polymerase chain reaction (qPCR) to confirm the microarray findings. Our results indicate several genes of interest, and have illustrated differences between fish and mammals that may be key to understanding failure of CNS regeneration in mammals. These findings have been presented and published as indicated in this report, and have supported 3 major grant proposals (one successful, one declined, and one pending).