LAMINAR SPECIFIC ATTACHMENT AND NEURITE OUTGROWTH OF THALAMIC NEURONSON CULTURED SLICES OF DEVELOPING CEREBRAL NEOCORTEX

In nervous system development, the growth cones of advancing axons are thought to navigate to their targets by recognizing cell-surface and extracellular matrix molecules that act as specific guidance cues. To identify and map cues that guide the growth of a particular axonal sys tem, the thalamocortical afferents, an assay was devised to examine sh ort-term interactions of dissociated embryonic thalamic cells with liv ing, similar to 150 mu m slices of developing mouse forebrain. Thalami c cells rapidly (<3 hours) and efficiently attached to and extended ne urites on pre- and postnatal slices, but a broad zone throughout the n eocortex was generally non-permissive for both thalamic cell attachmen t and the ingrowth of neurites. This zone coincided with the cortical plate at early stages (embryonic day 15), but later became restricted, in rostral-to-caudal fashion, to cortical laminae 2/3. Thus, at each stage, thalamic cells in vitro avoided just that area that thalamic ax ons confront, but generally do not enter, in vivo. In addition, neurit es that extended on some layers were found to be significantly oriente d in directions that coincide with the pathways that thalamic axons fo llow in vivo. These results imply that local adhesive cues and signals that affect process outgrowth are distributed among developing cortic al laminae in a manner that could underlie much of the temporal and sp atial patterning of thalamocortical innervation.