FUNCTIONS OF BRAIN CHONDROITIN SULFATE PROTEOGLYCANS DURING DEVELOPMENT - INTERACTIONS WITH ADHESION MOLECULES

Chondroitin sulfate proteoglycans (CSPGs), including neurocan and phos phacan, are believed to be major components of brain extracellular mat rix that interact with other matrix proteins and cell surface receptor s. In addition, several brain CSPGs such as receptor protein tyrosine phosphatase beta are expressed as cell surface receptors that interact with proteins in the extracellular matrix and with receptors on neura l cells. Recent in vitro studies demonstrate that, although the brain CSPGs neurocan and phosphacan can promote transient adhesion of neuron al cells, they inhibit stable cell adhesion and neurite growth promote d by the cell adhesion molecule Ng-CAM/L1. Neurocan and phosphacan bin d with high affinity to Ng-CAM/L1 and N-CAM which may be their major r eceptors on neurons. These CSPGs also bind to other adhesion molecules , such as tenascin-C, and can differentially modulate adhesion of glia to tenascin-C, Both the glycosaminoglycan and the core glycoproteins contribute to the function of the brain CSPGs. When expressed in regio ns containing low levels of adhesion molecules, various CSPGs includin g phosphacan, neurocan, versican, aggrecan, and NG2 proteoglycan may a ct as barriers to cell migration and axonal growth. In regions contain ing high levels of adhesion proteins, brain CSPGs may still act to mai ntain certain boundaries while allowing selective axonal extension to proceed. There are numerous regions of overlap in the expression patte rns of CSPGs and adhesion molecules in vivo, and the relative levels o f these molecules as well as the organization of the extracellular mat rix may be important factors that regulate the rate of axonal growth l ocally. Differential expression of CSPGs may be important for modulati ng cell adhesion as well as axonal growth and guidance during neural d evelopment, and continued expression may prevent these processes in th e normal mature nervous system as well as following brain injury.