INHIBITORS AND PROMOTERS OF THALAMIC NEURON ADHESION AND OUTGROWTH INEMBRYONIC NEOCORTEX - FUNCTIONAL ASSOCIATION WITH CHONDROITIN SULFATE

When embryonic thalamic neurons are plated onto living slices of mouse forebrain, cell attachment and neurite outgrowth on different layers of the developing cerebral cortex vary dramatically, in ways that corr elate with the timing and pattern of thalamocortical innervation. Thes e layer-specific differences can be eliminated from embryonic day 16 s lices by enzymatic removal of chondroitin sulfate (CS). The cortical p late (a zone avoided by thalamic axons in vivo) possesses inhibitory a ctivity (anti-adhesive, neurite repelling) and the intermediate zone a nd subplate (in which thalamic axons normally grow) possess stimulator y activity (adhesive, neurite promoting), both of which are chondroiti nase sensitive. These opposing activities appear not to reflect the pr esence of different CS proteoglycans (CSPGs) in different zones, but r ather the presence of differentially localized CS-binding molecules, w hich can be competed away by soluble CS. This model reconciles conflic ting reports on the actions of CSPGs in neural development, and sugges ts a role for CSPGs in the organization of matrix-bound cues in the br ain.