Cell-cell and Cell-extracellular matrix interactions appear to play a major role in the histogenesis of the nervous system. Despite our detailed knowledge of the sequence of these events, little is known about the mechanisms that control them. This is particularly crucial in the nervous system where impaired neuronal migration results in severe deficits of both form and function. In the current investigation we propose to examine one such extracellular matrix component, thrombospondin, which appears to have a unique distribution in the developing nervous system. We will first determine the temporal and spatial pattern of distribution of TSP during neurulation, neural crest migration and formation of the cerebellar cortex using light and transmission electron microscope immunocytochemistry. In situ hybridization studies will be carried out to determine the pattern of cellular synthesis of TSP. Finally, to determine if TSP plays a functional role in development of the nervous system, we will attempt to inhibit these processes with anti-TSP antibodies or its recombinant heparin binding domain using whole embryo culture or slice culture techniques. This integrative approach should determine both the role of a unique extracellular matrix component, thrombospondin, in the early development of the nervous system and produce valuable new data on the mechanisms involved in cell-cell interactions and cell migrations involved in this process.
