Combinatorial process for extracellular matrix influences on gene expression: a hypothesis.

The extracellular matrix (ECM) has a number of influences on gene expression during growth and development. Cellular and tissue interactions among similar and dissimilar cell types result in the production of complex and fascinating extracellular matrices throughout development. This paper presents a hypothesis that will emphasize those examples in which the extracellular matrix mediates de novo gene expression termed "determination" of a unique phenotype. It will be found that a number of gene families within the eucaryotic genome can be preferentially activated during the course of differentiation-specific protein expression. Results from a number of laboratories illustrate that close-range and/or short-range cell-cell interactions invoke preferential differentiation-specific protein synthesis and accumulation during embryogenesis. This discussion will highlight how the extracellular matrix microenvironment of a particular population of cells invokes irreversible, differentiation-specific gene expression. Recent advances in the isolation and characterization of a large number of different extracellular matrix macromolecules (eg various types of collagens, fibronectin, chondronectin, osteonectin, laminin, proteoglycans, enamel protein) now suggest a renewed interest in this problem area, and also the promise for significant breakthroughs in the near future. The combinatorial hypothesis for extracellular matrix influences on gene expression states that changing, rearranging, or altering the macromolecular constituents within ECM results in a myriad diversity in developmental instructions. The hypothesis predicts that no individual morphogen is required.