Reelin Does Not Directly Influence Axonal Growth

Reelin is a large extracellular glycoprotein involved in the development of architectonic patterns, particularly in the cerebral cortex and hippocampus, where it is synthesized primarily by Cajal-Retzius cells. In the hippocampus, Reelin also regulates the growth and/or distribution of afferent entorhinal and commissural axons. To assess further the possible action of Reelin on axonal growth, we used the three-dimensional collagen gel assay to measure axonal elongation from reeler cortical explants in the presence of Reelin. Because Reelin is proteolytically processed in vivo, normal explants and Reelin-transfected human embryonic kidney 293T cells were used, respectively, as sources of processed and full-length protein. The reliability of the assay was tested by demonstrating a clear repulsive action of semaphorin 3F (p < 0.0001). However, neither full-length nor processed Reelin exhibited any significant attraction or repulsion on cortical axons. Our results suggest that the reported effects of Reelin on axonal pathways are indirect, secondary to the architectonic disturbances that result from Reelin deficiency, and that the effects of Cajal-Retzius cells on connectivity are primarily independent of Reelin.