A diverse set of proteoglycans, the major component of extracellular matrix (ECM), is constitutively expressed in developing and adult brain. This is in stark contrast to the fact that most other ECM components including fibronectin, laminin, collagens, an tenascin are not expressed or are only transiently expressed during development in the brain parenchyma. This suggests that proteoglycans may play a major functional role in cell-cell and cell-matrix interactions in the brain. By employing an approach using polyclonal antibodies which recognize multiple proteoglycans core proteins, we have identified and molecularly cloned a novel chondroitin sulfate proteoglycan in the brain. This proteoglycan, named """"""""brevican"""""""", is a member of the aggrecan/versican family, containing a hyaluronic acid-binding domain in its N-terminus and a lectin-like domain in its C-terminus. Among this family of proteoglycans, brevican has the smallest core protein and appears to be the most abundant in the postnatal brain. Expression of brevican is highly specific in the brain and greatly increases as the brain develops. These results suggest that brevican may play a role in cell-cell or cell-matrix interaction during development of the nervous system. Thus, the specific aims of this proposal are; 1) to determine the spatiotemporal expression pattern of brevican in the developing nervous system; 2) to define the molecular interactions of brevican by identifying brevican-binding proteins; and 3) to determine the effect of brevican in neurite outgrowth and in neuron-glia interaction in vitro. Our long-term objective is to elucidate the role of brevican in the development of the nervous system. Since proteoglycans have been implicated in the formation of amyloid plaques in Alzheimer's disease, these studies could also contribute to understanding the mechanism of amyloid deposition and the progression of neurodegenerative processes.
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