Time-dependent changes in the expression of the MEF2 transcription factor family during topographic map reorganization in mammalian visual cortex.

Removal of retinal input from a restricted region of adult mammalian visual cortex leads to a substantial reorganization of the retinotopy within the lesion projection zone (LPZ) of primary visual cortex (area 17). Little is known about the molecular mechanisms underlying such cortical plasticity. We investigated whether small but homonymous central retinal lesions induced differences in gene expression patterns between central area 17, the LPZ, vs. peripheral area 17 of the adult cat. Systematic differential mRNA display screening revealed higher levels for the mRNA encoding the transcription factor MEF2A in the LPZ. Semi-quantitative PCR confirmed this dependency of mef2A mRNA expression on visual eccentricity in area 17 of animals with retinal lesions in contrast to normal animals. Western blotting experiments extended these data to the protein level and to two other members of the MEF2 transcription factor family, i.e. MEF2C and MEF2D. Quantitative analysis of the Western blotting experiments further revealed a post-lesion survival time-dependent change in expression for all three MEF2 family members. The lesion effect was maximal at 3 days and 1 month post-lesion, but only minor at 2 weeks post-lesion. Interestingly, complete removal of retinal input from area 17 by surgery did not significantly alter the expression of the MEF2 transcription factors, excluding a definite correlation between neuronal activity and MEF2A expression levels. MEF2A immunocytochemistry confirmed both qualitatively and quantitatively the Western blotting observations in all animal models. Together, our findings identified a brain plasticity-related expression pattern for the MEF2 transcription factor family in adult mammalian neocortex.