Young Versus Old CorticoSpinal Tract Neurons

This project is being run by Murray Blackmore with the assistance of Yania Martinez, Orisley Franch, and Zimei Wang, Ph.D..

Young CNS neurons have much greater regenerative capacity than old CNS neurons. Perhaps old neurons express genes that inhibit regeneration. Alternatively, perhaps old neurons fail to express genes that are required for regeneration. In reality, both hypothesis are likely to be true. We have used microarray data from corticospinal track neurons to generate a list of about 800 candidate genes that are differentially expressed during development. We have tested 757 clones from our library that correspond to about 60% of the genes in our list. We have identified 7 genes have a robust effect on neurite growth. Four of the genes enhance growth and three inhibit growth. Interestingly, the four that enhance growth show decreased expression as development proceeds and the three that inhibit axon growth show increased expression as the animal ages.

Plot of neurite length data from four plates tested during the screen. The red and green bars show two genes that give consistently have strong effects on cortical neuron neurite growth in vitro. We now use them as controls in all plates. The pink lines show thresholds of two standard deviations from the mean, the cut off we use to identify potential hits for rescreening.