Cell adhesion, migration, and morphogenesis are crucial events in craniofacial development, and errors in them can produce congenital anomalies. Specific structural molecules that mediate these processes and the mechanisms that regulate them are being identified and characterized in detail. Fibronectin and related molecules appear to be crucial for normal morphogenesis, e.g. for neural crest cell migration to form craniofacial structures. The regions of fibronectin that are essential for cell adhesion are being characterized in detail by site- directed mutagenesis and sequence homology scanning approaches. A 5 amino acid sequence in the 9th type III repeating unit has been tentatively identified as essential for cell adhesion mediated by the fibronectin receptor. Precise mapping of this site should facilitate the rational design of novel, specific bioadhesives and competitive inhibitors. Cell migratory interactions with extracellular molecules can be regulated by a novel regulatory phenomenon we have discovered termed """"""""contact stimulation of migration."""""""" Melanocytes and neural crest cells display 10-200 fold stimulation of migration rates after such cell-cell contact. The molecular mechanisms of this process are being pursued. Another mechanism for regulating cell migration involves cytokines such as scatter factor/hepatocyte growth factor and its c-met proto-oncogene receptor. We have sequenced mouse scatter factor, which has 90% amino acid sequence identity with its human homologue. The mRNA for this molecule can be detected in substantial quantities in 9-10 day mouse embryos, suggesting that it may play roles in developmental regulation of cell type and migration. The corresponding mouse c-met receptor cDNA has also been cloned. We have discovered a novel spliced version of this receptor that may have distinct regulatory properties, a possibility that is being tested using an expression system to compare standard and alternatively spliced products. These studies should provide a molecular understanding of how the complex but important processes of cell migration during embryogenesis are regulated.
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