In the Gram negative soil bacterium Myxococcus xanthous, environmental cue such as nutrient limitation initiate a developmental phase culminating in the formation of a multicellular structure, the fruiting body, followed by the differentiation of growing cells into metabolically-quiescent spores. After initiation by environmental signals, this developmental process is subsequently regulated by a series of cell-derived extracellular signals and cell-cell interactions. The goal of this proposal is to determine how cells sense nutrient limitation and process this information to initiate fruiting body development. In M. xanthous (p)ppGpp is both necessary and sufficient for the initiation of the developmental program, suggesting that this regulatory nucleotide is central to the mechanism of starvation-recognition. In addition a collection of Tn5lac reporter fusions provides tools to measure how this signaling system controls developmental gene expression. One such reporter fusion is (4408 which is key to this study because it is controlled by starvation and defines an operon from which one or more products is essential for the coupling of early starvation signals to subsequent developmental events. We have named the locus defined by (4408 as sde, starvation inducible, development essential. The purpose of the proposed research is to: 1) identify the genes and their products that regulate the level of the starvation signal, (p)ppGpp; and 2) determine how the developmental signal is propagated once initiated by the starvation-recognition signal transduction pathway. Specifically, the genes which regulate the intracellular levels of (p)ppGpp will be identified. In addition, the cis acting regulators controlling sde expression will be identified. Finally, to gain insight into how the developmental signal is propagated, the function of the genes in the sde operon will be determined. This work addresses the mechanism of a basic and fundamental biological process: cell response to environmental and extracellular signals and how such interactions can lead to changes in cell behavior and morphology.
