Chondroitin sulfate proteoglycans in the developing cerebral cortex: The distribution of neurocan distinguishes forming afferent and efferent axonal pathways

Abstract

The first thalamocortical axons to arrive in the developing cerebral cortex traverse a pathway that is separate from the adjacent intracortical pathway for early efferents, suggesting that different molecular signals guide their growth. We previously demonstrated that the intracortical pathway for thalamic axons is centered on the subplate (Bicknese et al. [1994] J. Neurosci. 14:3500-3510), which is rich in chondroitin sulfate proteoglycans (CSPGs; Sheppard et al. [1991] J. Neurosci. 11:3928-3942), whereas efferent axons cross the subplate to exit in a zone containing much less CSPG. To define the molecular composition of the subplate further, we used antibodies against CSPG core proteins and chondroitin sulfate disaccharides in an immunohistochemical analysis of their distribution in the developing neocortex of the rat. Immunolabeling for neurocan, a central nervous system-specific CSPG (Rauch et al. [1992] J. Biol. Chem. 267:19537-19547), and for chondroitin 6-sulfate and unsulfated chondroitin becomes prominent in the subplate before the arrival of thalamic afferents. Immunolabeling is initially sparse in the cortical plate but appears later in maturing cortical layers. A postnatal decline in immunolabeling occurs uniformly for most proteoglycans, but, in the somatosensory cortex, labeling for neurocan, phosphacan, and chondroitin 4- and 6-sulfate declines in the centers of the whisker barrels before the walls. In contrast to neurocan, immunolabeling for other proteoglycans is either uniformly distributed (syndecan-1, N-syndecan, 5F3, phosphacan, chondroitin 4-sulfate), restricted to axons (PGM1), distributed exclusively on nonneuronal elements (2D6, NG2, and CD44), or undetectable (9. 2. 27, aggrecan, decorin). Thus, neurocan is a candidate molecule for delineating the intracortical pathway of thalamocortical axons and distinguishing it from that of cortical efferents.