LAGC-NULL AND GBF-NULL CELLS DEFINE KEY STEPS IN THE MORPHOGENESIS OFDICTYOSTELIUM MOUNDS

The transition to multicellularity is a key feature of the Dictyosteli um life cycle, and two genes, gbf and lagC, are known to play pivotal roles in regulating this developmental switch. lagC-null and gbf-null cells fail to induce cell-type-specific genes ordinarily expressed dur ing multicellular development. The null mutants also share a similar m orphological phenotype: mutant cells repeatedly aggregate to form a lo ose mound, disperse, and reform a mound, rather than proceeding to for m a tip. To characterize defects in morphogenesis in these mutants, we examined cell motion in the mutant mounds. In analogy with the failed transition in gene expression, we found that lagC-null and gbf-null m ounds failed to make a morphogenetic transition from random to rotatio nal motion normally observed in the parent strain. One reason for this was the inability of the mutant mounds to establish a single, dominan t signaling-wave center. This defect of lagC-null or gbf-null cells co uld be overcome by the addition of adenosine, which alters cAMP signal ing, but then even in the presence of apparently normal signaling wave s, cell motility was still aberrant. This motility defect, as well as the signaling-wave defect, could be overcome in lagC-null cells by ove rexpression of GBF, suggesting that lagC is dispensable if GBF protein levels are high enough. This set of morphogenetic defects that we hav e observed helps define key steps in mound morphogenesis. These includ e the establishment of a dominant signaling-wave center and the capaci ty of cells to move directionally within the cell mass in response to guidance cues. (C) 1998 Academic Press.