Cell adhesion, cell migration, and specific morphogenetic events are crucial processes in normal embryonic and fetal development, and errors in them can produce anomalies. Specific structural molecules that mediate these processes and the mechanisms that regulate them are being identified and characterized. Fibronectin and related molecules are thought to be crucial for normal morphogenesis, e.g. for neural crest cell migration. Regions of fibronectin required for cell adhesion are being characterized in detail by site-directed deletion and biological analysis of synthetic peptide inhibitors. Our recent studies demonstrate requirements for helper or synergy regions for the functions of both the central cell-binding domain and the alternatively spliced IIICS regions of fibronectin. Such synergy regions cooperate with the short tripeptide sequences Arg-Gly-Asp and Leu-Asp-Val, increasing their activities up to 20-100 fold. The mechanisms of synergy site function in cell adhesion and migration are being analyzed by fibronectin- fibronectin and fibronectin-vitronectin chimeras, as well as by studies of variant synthetic peptides. The functions of another matrix molecule that we found to contain a biologically active Arg-Gly-Asp sequence, type XII collagen, are being analyzed and compared to fibronectin by monoclonal antibodies. Cell migratory interactions with extracellular molecules can be regulated by a novel process we have discovered and termed """"""""contact stimulation of migration."""""""" Neural crest cells or derivatives can show up to 200-fold stimulation of migration after such contact. In addition, cytokine receptors such as the c-met proto- oncogene product can also regulate migration. Molecular requirements for function of these regulatory mechanisms are under investigation.
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