THALAMOCORTICAL AXONS EXTEND ALONG A CHONDROITIN SULFATE PROTEOGLYCAN-ENRICHED PATHWAY COINCIDENT WITH THE NEOCORTICAL SUBPLATE AND DISTINCT FROM THE EFFERENT PATH

The distinct axonal tracts of the mature nervous system sie defined du ring development by sets of substrate-bound and diffusible molecular s ignals that promote or restrict axonal elongation. In the adult cerebr al cortex, efferent and afferent axons are segregated within the white matter. To define the relationship of growing efferent and afferent a xons in the developing murine cortex to chondroitin sulfate proteoglyc ans (CSPGs) in the pericellular and extracellular matrix, we used the fluorescent tracer Dil to determine axonal trajectories and immunolabe ling to disclose the distribution of CSPGs. Axons of neurons in the pr eplate are the first to leave the cortex; they arise in the CSPG-rich preplate and extend obliquely across it to enter the CSPG-poor interme diate zone. Slightly later, axons of cortical plate neurons extend dir ectly across the CSPG-rich subplate, and then turn abruptly to run in the upper intermediate zone. In contrast, once afferent axons from the thalamus reach the developing cortical wall, their intracortical traj ectory is centered on the CSPG-rich subplate, above the path taken by efferent axons. Our findings demonstrate a molecular difference betwee n the adjacent but distinct efferent and afferent pathways in developi ng neocortex. Early efferents cross the subplate and follow a pathway that contains very little CSPG, while afferents preferentially travel more superficially within the CSPG-rich subplate. Thus, CSPGs and asso ciated extracellular matrix (ECM) components in the preplate/subplate do not form a barrier to axonal initiation or outgrowth in the neocort ex as they may in other locations. Instead, their distribution suggest s a role in defining discrete axonal pathways during early cortical de velopment.