New properties of motor protein dependent transport in the axonal guidance of the telencephalic axonal tracts

SAEZ, TMM; OTERO, M G; ALLOATTI, M; CROMBERG, L E; POZO DEVOTO, V M; GELMAN, D; FALZONE, TL

Cordoba

Congreso; XXIX SAN Annual Meeting; 2014

Wiring of the brain relies, at first, on the correct outgrowth of axons to reach the appropriate target area and establish synaptic contact with correct cells. Several guidance receptors present in the surface of axonal growth cones read and execute directional cues present in the extracellular environment of the navigating growth cone. The exact timing, levels, and localization of expression of the guidance receptors in the growth cone therefore determine the outcome of guidance decisions. Membrane trafficking and cargo delivery are essential in developing neurons for delivering molecules that are required for elongation and guidance of the growing axonal. To test the hypothesis that axonal transport impairment can cause axonal guidance defects in the major axonal tracts, we use mice lacking the kinesin light chain 1(KLC1) subunit of the anterograde motor kinesin-1. KLC1-/- postnatal mouse brain exhibited dysgenesis of the corpus callosum, anterior commisure and internal capsule. Using carbocyanine tracer labeling and immunofluorescence staining for L1-CAM, we found that a population of callosal axon fail to cross the midline in KLC1-/- mice, forming a rudimentary corpus callosum. In addition, a subset of corticothalamic axons was misrouted or fails to cross the cortico-striatal boundary in KLC1-/- neonatal brain. These results suggest that KLC1 is required for the pathfinding and axonal guidance of the developing telencephalic axonal tracts in the developing brain.