DUAL-ACTION OF A CARBOHYDRATE EPITOPE ON AFFERENT AND EFFERENT AXONS IN CORTICAL DEVELOPMENT

During development of the mammalian cerebral cortex, ingrowing afferen ts from the thalamus take a path that is different from that of axons leaving the cortical plate. Thalamic axons arrive al the cortex at the time before their target cells of layer 4 are generated in the ventri cular zone, but they invade the cortex only shortly before these cells have migrated to their final position in the cortex. Growth-promoting molecules are upregulated in the developing cortical plate during thi s period. To identify such molecules, we have generated monoclonal ant ibodies against membrane preparations from rat postnatal cortex. In We stern blots, one antibody (mAb 10) recognized a carbohydrate epitope o f a glycoprotein with an apparent molecular weight extending from 180 to 370 kDa. Immunohistochemical staining revealed that the staining pa ttern of mAb 10 at embryonic stages delineates the pathway of thalamoc ortical axons, with only very faint labeling of the corticofugal pathw ay. In vitro assays in combination with time-lapse imaging indicated t hat mAb 10 has opposite effects on the growth of thalamic and cortical axons. The growth speed and axonal elongation of thalamic fibers on p ostnatal cortical membranes preincubated with mAb 10 was reduced compa red with untreated cortical membranes. In contrast, cortical axons gre w faster and stopped their growth less frequently after addition of mA b 10 to a cortical membrane substrate. Taken together, these results s uggest that a carbohydrate moiety of a membrane-associated glycoprotei n plays a role in the segregation of afferent and efferent cortical ax ons in the white matter. Moreover, the epitope recognized by mAb 10 mi ght also contribute to regulation of the timing of the thalamocortical innervation at later developmental stages.