tip genes act in parallel pathways of early Dictyostelium development.

Analysis of Dictyostelium strains carrying null mutations in tipA showed a primary defect in cell sorting and the formation of tips on the developing mound. To study the process affected in tipA- mutants further, other mutants with a similar phenotype were isolated and characterized. These studies showed three new Dictyostelium genes: tipB, tipC, and tipD. All the tip mutants aggregate into larger than average mounds, which split up and form many lips on their surfaces. Furthermore, each mutant exhibits reduced or aberrant cell-sorting behavior, never makes migrating slugs, and has severely reduced fruiting body and spore production. The mRNA of each tip gene is present in vegetative cells and does not vary significantly with development. Prespore and prestalk gene expression is reduced or delayed in the tip mutants indicating cell type differentiation is dependent on the function of these genes. Developing mutant cells in chimeric mixtures with wildtype cells demonstrated that the defects in each tip mutant behave cell autonomously. The overexpression of TipA in a tipB- background and the overexpression of TipB in a tipA- background significantly improved the morphogenesis of these mutants. These were the only situations in which the expression of one tip gene could compensate for the lack of a different tip gene. Except for the tipA-/tipB- strain, double mutations in the tip genes have additive effects, causing a more severe mutant phenotype with defects earlier in development than single mutants. The tipA-/tipB- double mutant does not show additive effects and is very similar to the tipA-single mutant. Analysis of the effects of double mutations and overexpression indicates that members of this class of genes appear to act through parallel pathways of differentiation and tip formation in early Dictyostelium development. Furthermore, TipA and TipB appear to have some overlapping functions or are involved in the same pathway. The multitipped phenotype observed in all the mutants may be a general result of perturbing early developmental events such as cell type differentiation and cell type proportioning.