Control of Co-ordinated Cell Movement during Morphogenesis: Experiments And Models

Thursday, September 10, 1998 - 9:00am - 10:00am
Keller 3-180
Cornelius Weijer (University of Dundee)
Cell movement plays an important role in morphogenetic processes such as gastrulation, neurulation and formation of the brain. Its co-ordination most likely requires long range signalling, however little is known about the signals and mechanisms involved. We study the control of differential cell movement in an evolutionary simple organism, the cellular slime mould Dictyostelium discoideum which stands on the threshold between unicellular and multicelluar life. At the vegetative stage the cells live as solitary amoebae in the soil, which feed on bacteria and multiply by binary fission. However under starvation conditions a multicellular developmental cycle is induced in which up to 100,000 cells aggregate chemotactically towards an aggregation centre to form a slug which then can move to a new habitat where it forms a fruiting body, consisting of a stalk supporting a spore head. The spores germinate and the cycle starts again. During aggregation the cells communicate over large distances via propagating waves of the chemoattractant cyclic AMP. These waves are initiated in the aggregation centre and propagate outwards as concentric or spiral waves, instructing the cells to move towards the aggregation centre. We have developed digital image processing methods to analyse the dynamics of the wave propagation (cell-cell communication) process in vivo. Novel image processing methods allow us to track individual transformant cells expressing the green fluorescent protein GFP as a cell type specific reporter gene. We analyse changes in speed and direction of cell movement as well as changes in cell shape at the single cell level in a multi cellular organism. We have now shown that the same principles that govern aggregation, i.e. spiral wave propagation and chemotactic cell movement, also control the morphogenesis of the later developmental stages. The mounds are characterised by multi-armed spirals while in slugs the chemotactic signal propagates as a three dimensional spiral wave in the front and transforms into planar waves in the back. This transformation in wave shape results from differences in the excitability of the prestalk and prespore cell types located in the front and the back of the slug respectively. These cells types arise first in random positions in the mound and then sort out chemotactically to form an axial pattern in the slug. This cell sorting then feeds back onto the wave propagation system. We perform detailed model calculations to understand how such complex wave forms can arise in three dimensional excitable media and how the cell movement feeds back on the pattern of wave propagation. This has given us some insight in the basic cellular principles of multi-cellular cell sorting, i.e. cell type specific differences in excitability as well as differences in chemotactic responsiveness.

We are now analysing the consequences of perturbations of the signalling mechanism on morphogenesis via the study wave propagation and cell movement in cAMP receptor, G protein and chemotaxis and motility mutants.