Modeling chemotactic cell sorting during Dictyostelium discoideum mound formation

Coordinated cell movement is a major mechanism of the multicellular develop ment of most organisms. The multicellular morphogenesis of the slime mould Dictyostelium discoideum, from single cells into a multicellular fruiting b ody, results from differential chemotactic cell movement. During aggregatio n cells differentiate into prestalk and prespore cells that will form the s talk and spores in the fruiting body. These cell types arise in a salt and pepper pattern after what the prestalk cells chemotactically sort out to fo rm a tip. The tip functions as an organizer because it directs the further development. It has been difficult to get a satisfactory formal description of the movement behavior of cells in tissues. Based on our experiments, we consider the aggregate as a drop of a viscous fluid and show that this con sideration is very well suited to mathematically describe the motion of cel ls in the tissue. We show that the transformation of a hemispherical mound into an elongated slug can result from the coordinated chemotactic cell mov ement in response to scroll waves of the chemoattractant cAMP. The model ca lculations furthermore show that cell sorting can result from differences i n chemotactic cell movement and cAMP relay kinetics between the two cell ty pes. During this process, the faster moving and stronger signaling cells co llect on the top of the mound to form a tip. The mound then extends into an elongated slug just as observed in experiments. The model is able to descr ibe cell movement patterns in the complex multicellular morphogenesis of Di ctyostelium rather well and we expect that this approach may be useful in t he modeling of tissue transformations in other systems.