Live cell imaging of cell movement and transdifferentiation during regeneration of an amputated multicellular body of the social amoeba Dictyostelium discoideum.

The regeneration of lost body parts is a fascinating phenomenon exhibited by some multicellular organisms. In social amoebae, such as Dictyostelium discoideum, the pseudoplasmodium is a temporary migratory multicellular structure with high regeneration ability. It consists of future stalk cells (prestalk cells) at the anterior end and future spore cells (prespore cells) at the posterior end, and if amputated, the remaining cells can rapidly regenerate the lost portion within several hours. Details of this regeneration event have been extensively documented; however, little is known about the behavior of individual cells involved in this process. In this study, we performed live cell imaging of cell behavior during regeneration of the excised anterior prestalk region. We used cells that specifically express GFP in the prestalk cell lineage to examine how the prestalk region is regenerated after this region is excised. The current model of prestalk regeneration suggests that the progenitors of prestalk cells, known as anterior-like cells (ALCs), which are sparsely distributed in the prespore region, are redistributed to form the new prestalk region. However, we found that the regenerated prestalk region was formed mainly by the transdifferentiation of prespore cells surrounding the excised anterior end, with little clustering of pre-existing ALCs. Furthermore, the movement of randomly distributed labeled cells during regeneration revealed that although the posterior end was deformed and rounded in shape, the relative position of cells along the anterior-posterior axis remained largely unchanged. These results suggest that the original anterior-posterior axis is maintained in posterior bodies and that prespore cells at the anterior side transdifferentiate and regenerate the prestalk region.

Stable territory formation in ecology and its potential generality in pattern formations.

Stable territory formation is frequently observed in ecology. Until now, only the reaction-diffusion scheme has successfully produced stable patterns in the predator-prey system. However, it is a density-based scheme and in principle it cannot be used to derive a comprehensive understanding from a mean-field scheme. The application of our new stochastic individual-based scheme to predator-prey systems successfully produced stable patterns such as net, stripe, and lattice patterns for the first time. This study clearly shows that non-interacting time is an important factor in stable pattern formation. Specifically, of high importance is the existence of finite time to build the appetites of predators. In some cases, extreme increases of the appetites of predators lead to chaotic changes of the population, which are similar to the locust outbreak in Africa.

Cell-to-cell coordination for the spontaneous cAMP oscillation in Dictyostelium.

We propose a new cellular dynamics scheme for the spontaneous cAMP oscillations in Dictyostelium discoideum. Our scheme seamlessly integrates both receptor dynamics and G-protein dynamics into our previously developed cellular dynamics scheme. Extensive computer simulation studies based on our new cellular dynamics scheme were conducted in mutant cells to evaluate the molecular network. The validity of our proposed molecular network as well as the controversial PKA-dependent negative feedback mechanism was supported by our simulation studies. Spontaneous cAMP oscillations were not observed in a single mutant cell. However, multicellular states of various mutant cells consistently initiated spontaneous cAMP oscillations. Therefore, cell-to-cell coordination via the cAMP receptor is essential for the robust initiation of spontaneous cAMP oscillations.

A molecular network underlying spontaneous cAMP oscillation and synchronization in Dictyostelium.

We propose a molecular network, incorporating both adaptation and phosphorylation, to account for the spontaneous cAMP oscillation of Dictyostelium discoideum. We have modified the scheme previously proposed by Loomis and his collaborators so as to include adaptation by the cAMP receptor and such that extracellular cAMP is formed by the secreted intracellular cAMP instead of being directly produced by adenylyl cyclase. Furthermore, our scheme provides better robustness, and can be applied to spontaneous cAMP production by a cluster of cells.

Phase transitions in predator-prey systems.

The relationship between predator and prey plays an important role in ecosystem conservation. However, our understanding of the principles underlying the spatial distribution of predators and prey is still poor. Here we present a phase diagram of a predator-prey system and investigate the lattice formation in such a system. We show that the production of stable lattice structures depends on the limited diffusion or migration of prey as well as higher carrying capacity for the prey. In addition, when the prey's growth rate is lower than the birth rate of the predator, global prey lattice formation is initiated by microlattices at the center of prey spirals. The predator lattice is later formed in the predator spirals. But both lattice formations proceed together as the prey growth rate increases.

Modeling of the gap junction of pancreatic ß-cells and the robustness of insulin secretion.

Pancreatic ß-cells are interconnected by gap junctions, which allow small molecules to pass from cell to cell. In spite of the importance of the gap junctions in cellular communication, modeling studies have been limited by the complexity of the system. Here, we propose a mathematical gap junction model that properly takes into account biological functions, and apply this model to the study of the ß-cell cluster. We consider both electrical and metabolic features of the system. Then, we find that when a fraction of the ATP-sensitive K+ channels are damaged, robust insulin secretion can only be achieved by gap junctions. Our finding is consistent with recent experiments conducted by Rocheleau et al. Our study also suggests that the free passage of potassium ions through gap junctions plays an important role in achieving metabolic synchronization between ß-cells.

A new stochastic individual-based model for pattern formation and its application to predator-prey systems.

Reaction-diffusion theory has played a very important role in the study of pattern formation in biology. However, a group of individuals is described by a single state variable representing population density in reaction-diffusion models, and interaction between individuals can be included only phenomenologically. In this paper, we propose a new scheme that seamlessly combines individual-based models with elements of reaction-diffusion theory and apply it to predator-prey systems as a test of our scheme. In the model, starvation periods and the time to reproductive maturity are modeled for individual predators. Similarly, the life cycle and time to reproductive maturity of an individual prey are modeled. Furthermore, both predators and prey migrate through a two-dimensional space. To include animal migration in the model, we use a relationship between the diffusion and the random numbers generated according to a two-dimensional bivariate normal distribution. Despite the simplicity of this model, our scheme successfully produces logistic patterns and oscillations in the population size of both predator and prey. The peak for the predator population oscillation lags slightly behind the prey peak. The simplicity of this scheme will aid additional study of spatially distributed negative-feedback systems.

Receptors as a master key for synchronization of rhythms.

A simple, but general, scheme to achieve synchronization of rhythms is proposed. It can handle both external synchronization and self-synchronization within a single mathematical framework. In this scheme, external linear stimulations can be converted into internal nonlinear stimulations by the mathematical model receptor without breaking the regular motions of limit cycle oscillators. Thus, even a small external periodic stimulation can work very efficiently for achieving synchronization. Stimulation via model receptors is much more effective for synchronization than mechanically forced stimulations, and the phenomenon called N:M phase locking (N not equal to 1, M not equal to 1) can be suppressed in the weak coupling domain, too.