Fruiting body formation in Myxococcus xanthus: Pattern formation by a cell surface-associated morphogen

In response to starvation Myxococcus xanthus cells initiate a multicellular developmental program that culminates in the formation of spore-filled fruiting bodies. Fruiting body formation involves two morphogenetic processes, aggregation and sporulation, which are coordinated in time and space: aggregation of cells precedes sporulation and cells do not sporulate until they have accumulated inside the fruiting bodies. The starting point in the formation of fruiting bodies is a nearly symmetric distribution of cells in a homogeneous mat, and the endpoint is the asymmetric distribution of cells inside the multicellular fruiting bodies. The mechanism underlying this redistribution of cells is changes in organised cell movements from swarming in non-starving cells to aggregation in starving cells. Key questions in understanding fruiting body formation are how the aggregation process is accomplished and how aggregation and sporulation are coordinated. The intercellular C-signal has a key role in inducing and choreographing the aggregation process and in coordinating aggregation and sporulation.

To understand how the C-signal acts at the molecular level, we have analysed the mechanism of the C-signal. The C-signal is cell surface-associated and signal transmission occurs by a contact-dependent mechanism. C-signal accumulates during development. C-signal induces aggregation and sporulation at specific thresholds: at intermediate levels aggregation is induced and at high levels sporulation is induced. An ordered increase in the level of C-signalling in combination with the specific thresholds ensures the correct temporal order of aggregation and sporulation. The contact-dependent signal transmission mechanism allows the spatial coordination of aggregation and sporulation by coupling cell position and signalling levels.

To understand how the C-signal induces aggregation, we have analysed the effect of the C-signal on cell behaviour using fluorescence time-lapse video microscopy. The C-signal induced motility response includes increases in transient gliding speeds and in the duration of gliding intervals and decreases in stop and reversal frequencies. This response results in a switch in cell behaviour from an oscillatory to a unidirectional type in which the net-distance travelled by a cell per min is increased. We have proposed that the C-signal dependent regulation of the reversal frequency is essential to the aggregation process. We have proposed a qualitative model for aggregation. In this model, C-signal transmission is a local event, which occurs between two cells and without reference to the global pattern, and the result is a global organization of cells. This pattern formation mechanism does not require a diffusible substance or other actions at a distance.