Cell-Cell Contact Regulation of Differentiation

Berger, Edward

Abstract

As Dictyostelium cells aggregate to the multicellular state, they acquire the capacity for specific cell-cell recognition and cohesion. Specific cell-cell contact is a major signal controlling developmental gene expression, causing de-activation of one battery of coordinately expressed genes (the aggregative gene program), and activation of another (the post-aggregative gene program). The molecular basis for this switch s unknown. I propose to study the cell surface mechanisms by which specific cell-cell contact induces changes in gene expression. Specifically, I wish to learn whether any of the known cohesion molecules (discoidins I and II, gp80, gp150) are involved in this process. The proposed strategy will employ existing cloned DNA's to assay the expression of aggregative and post-aggregative genes. There are three main objectives: 1) To develop a system using isolated membrane ghosts added to living cells to mimic the regulatory effects of specific cell contact, 2) To examine the effects of purified cohesion molecules, or of reagents (antibodies and ligands) directed specifically against them, on the activities of the contact-regulated genes, and 3) To test the hypothesis that specific cell contact induces or maintains elevated intracellular levels of cAMP. These studies will make use of non-cohesive mutants isolated in my laboratory) which show aberrant expression of contact-regulated genes. The availability of antibodies against several known cohesion molecules, membrane ghosts from cells of varying cohesive specificities, mutants defective in specific cell contact, and cloned DNA probes against specific contact-regulated genes make this system uniquely accessible for studying cell contact regulation of developmental gene expression.