How amoeboids self-organize into a fruiting body: multicellular coordination in Dictyostelium discoideum

Abstract

When individual amoebae of the cellular slime mold Dictyostelium discoideum are starving, they aggregate to form a multicellular migrating slug, which moves toward a region suitable for culmination. The culmination of the morphogenesis involves complex cell movements that transform a mound of cells into a globule of spores on a slender stalk. The movement has been likened to a "reverse fountain," whereby prestalk cells in the upper part form a stalk that moves downwards and anchors to the substratum, while prespore cells in the lower part move upwards to form the spore head. So far, however, no satisfactory explanation has been produced for this process. Using a computer simulation that we developed, we now demonstrate that the processes that are essential during the earlier stages of the morphogenesis are in fact sufficient to produce the dynamics of the culmination stage. These processes are cAMP signaling, differential adhesion, cell differentiation, and production of extracellular matrix. Our model clarifies the processes that generate the observed cell movements. More specifically, we show that periodic upward movements, caused by chemotactic motion, are essential for successful culmination, because the pressure waves they induce squeeze the stalk downwards through the cell mass. The mechanisms revealed by our model have a number of self-organizing and self-correcting properties and can account for many previously unconnected and unexplained experimental observations.

Figure 1

Time sequence of a simulation of the process of culmination. The cell types are Psp (green), PstO (red), PstA (blue), St (cyan), Pf (magenta), Sl (yellow), and Tu (gray). The process is shown in MPEG Movie 1, which is published as supplemental data on the PNAS web site, www.pnas.org.

Figure 2

Detailed view of the stalk elongation during the simulation of Fig. 1. (Upper) Individual cells. Light bands indicate the regions of chemotactic motion toward cAMP. See also Movie 2, which is published as supplemental data on the PNAS web site, www.pnas.org. (Lower) Pressure differences, indicated by the mean cell volume of individual cells, averaged over five samples at intervals of 2 sec. Volumes are indicated by a color gradient from dark red (small volume) to bright yellow (large volume). (A) At 14 min and 40 sec. (B–E) With subsequent intervals of 40 sec. See also Movie 3, which is published as supplemental data.

Figure 3

Restoration of the direction of stalk elongation. Initially, the stalk tip is bent 90°. (A) 50 sec. (B) 8 min and 20 sec. (C) 16 min and 40 sec. See also Movie 4, which is published as supplemental data on the PNAS web site, www.pnas.org.

Figure 4

Snapshot, after 20 min, of two culminants orienting away from each other because of NH₃ production. (A) NH₃ distribution, indicated by a color gradient from dark red (low concentration) to bright yellow (high concentration), with blue bands of iso-concentration. See also Movie 5, which is published as supplemental data on the PNAS web site, www.pnas.org. (B) The culminants, with slanted stalks. Light bands indicate the cAMP waves. (C) Final configuration after 4 h. See also Movie 6, which is published as supplemental data.