Dictyostelium has a number of interesting timing characteristics including:1) the ability to rapidly recapitulate morphogenesis after disaggregation, 2) the ability to induce "erasure" and a program of dedifferentiation, 3) the ability to identify rate limiting steps or timers using conditional experiments, and 4) the ability to isolate specific timing mutants that have their individual rate limiting components altered. Dr. Alexander has recently characterized the mutant, FM-1, which has a specifically shortened preaggregative period. Conditional experiments demonstrate that this is due to the loss of the first rate limiting step. The cells progress through each subsequent developmental stage and form normal fruiting bodies. The mutation was mapped to linkage group II and is recessive to wild type. FM-1 and its derivatives show the remarkable property of rapid phenotypic switching. These strains can switch phenotypes at a rate of up to 100. The switch phenotypes include strains altered in timing, aggregation and morphogenesis. Dr. Alexander proposes to continue the investigations of developmental timing and phenotypic switching. He will: 1) phenotypically and genetically characterize timing mutants and the interactions of the genes, 2) determine whether rapid phenotypic switching can result in mutations in many different genes, 3) characterize a switching strain that is unique from the FM-1 switching system, 4) determine whether rapid phenotypic switching has characteristics that suggest that a mobile genetic element is the underlying molecular event, 5) attempt to demonstrate at the molecular level that high frequency switching in strain FM-1 and its derivatives is due to a transposable element. Identification of this element can lead to its use in transposon tagging for the generation of mutants and the isolation of the disrupted genes. %%% Temporal control is a central element of the developmental program of all organisms. The cellular slime mold Dictyostelium discoideum is a particularly good system for the study of the regulation of developmental timing. The timing of the morphogenetic stages is exquisitely synchronous and reproducible between experiments.
