Boundaries during normal and abnormal brain development: in vivo and in vitro studies of glia and glycoconjugates

This paper focuses on transient boundaries of glia and glycoconjugates during development of the mouse central nervous system (CNS). Lectin-bound glycoconjugates, glial fibrillary acidic protein, and the J1/tenascin glycoprotein are distributed coextensively within boundaries around developing substructural arrangements (e.g., developing nuclei, and at a finer level, somatosensory cortical "barrels" related to individual facial vibrissae) throughout the CNS during pattern formation events. Electron microscopy has shown that the J1/tenascin glycoprotein, for example, is present in immature astrocytes, on glial and neuronal plasma membranes, and within the pericellular space that could be extracellular matrix (ECM). The findings presented on the expression of this well-characterized ECM molecule suggest that previously described glial and glycoconjugate boundaries reported by our group are in part composed of specific recognition molecules. The J1/tenascin glycoprotein, a chondroitin sulfate-containing antigen termed the 473 proteoglycan, and the adhesion molecule on glia are expressed within discrete boundary regions and associated axonal pathways. There, they may sculpture fine aspects of functional cytoarchitectonic arrangements and help guide axons to specific targets. The expression and developmental regulation of glycoproteins such as J1/tenascin may thus be integral events during pattern formation and synaptogenesis in the CNS. The presence of abnormal glial arrangements and glycoconjugate boundaries in the cortices of the genetic mutant mouse reeler, and findings on plasticity of boundaries following various perturbations, suggest that boundary expression is controlled by both genetic and epigenetic factors. Some future directions for studying developmental boundaries, including use of cultured explants for in vitro "bioassays," are also discussed.