This study concerns the role of proteoglycans in nervous system development. Proteoglycans, proteins that bear distinctive polysaccharides known as glycosaminoglycans, are widely distributed on cell surfaces and in the extracellular matrix. Many studies suggest that proteoglycans play critical roles in development, and this is thought to reflect their involvement in cell-cell and cell-matrix interactions. In the developing nervous system in particular, there is evidence that proteoglycans are involved in a variety of cell behaviors. Moreover, a striking proportion of proteins believed to influence neural development interact specifically with glycosaminoglycans. To understand the specific roles of proteoglycans in neural development, their sites and mechanisms of action must be defined. Before this can be done, however, it will first be necessary to identify the proteoglycans that are present in the developing nervous system and obtain tools that can be used to manipulate their functions. The expression of proteoglycans will therefore be examined in rat brain at various developmental stages (from embryonic to adult) and in various brain regions. Proteoglycans with provocative patterns of developmental and regional expression will be identified and monoclonal antibodies that recognize them will be obtained. Immunohistochemical data on the location and timing of expression of such proteoglycans will be used to suggest developmental events in which they participate. This information will then be correlated with two functionally important membrane protein?) and binding to glycosaminoglycan-binding proteins (does the proteoglycan bind selectively to proteins thought to mediate developmental events occuring when and where the proteoglycan is expressed?). The information and reagents to be obtained through this work are needed in order that direct in vitro and in vivo tests of the roles of individual proteoglycans in nervous system development may be conducted. Such studies will provide insights into the molecular mechanisms of mammalian brain development and will be directly relevant to the pathogenesis and treatment of development abnormalities.
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