The role of L1 in axon pathfinding and fasciculation.

The neural cell adhesion molecule L1 has been found to play important roles in axon growth and fasciculation. Our main objective was to determine the role of L1 during the development of connections between thalamus and cortex. We find that thalamocortical and corticothalamic axons in mice lacking L1 are hyperfasciculated, a subset of thalamocortical axons make pathfinding errors and thalamocortical axon growth cones are abnormally long in the subplate. These defects occur despite formation of six cortical layers and formation of topographically appropriate thalamocortical connections. The loss of L1 is accompanied by loss of expression of ankyrin-B, an intracellular L1 binding partner, suggesting that L1 is involved in the regulation of Ank2 stability. We postulate that the pathfinding errors, growth cone abnormalities and hyperfasciculation of axons following loss of L1 reflect both a shift in binding partners among axons and different substrates and a loss of appropriate interactions with the cytoskeleton.