New functions of motor protein dependent transport in the axonal guidance

SAEZ T; FALZONE T

Huerta Grande, Cordoba

Congreso; XXIX congreso de la SAN; 2014

SAN

Wiring of the brain relies on the proper outgrowth of axons to reach the appropriate target area and to establish synaptic contacts with other neurons. Several guidance receptors present in the surface of axonal ends read and execute directional cues present in the extracellular environment of the navigating growth cone. Timing, levels, and localization of 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 required for elongation and guidance of the growing axon. 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 a population of callosal axon failing to cross the midline in KLC1-/- mice and developing  into 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 telencephalic axonal tracts in the developing brain