Pseudomonas aeruginosa is a monoflagellated bacterium that can use its single polar flagellum to swim through liquids and move collectively over semisolid surfaces, a behavior called swarming. ...Previous studies have shown that experimental evolution in swarming colonies leads to the selection of hyperswarming bacteria with multiple flagella. Here we show that the advantage of such hyperswarmer mutants cannot be explained simply by an increase in the raw swimming speed of individual bacteria in liquids. Cell tracking of time-lapse microscopy to quantify single-cell swimming patterns reveals that both wild-type and hyperswarmers alternate between forward and backward runs, rather than doing the run-and-tumble characteristic of enteric bacteria such as E. coli. High-throughput measurement of swimming speeds reveals that hyperswarmers do not swim faster than wild-type in liquid. Wild-type reverses swimming direction in sharp turns without a significant impact on its speed, whereas multiflagellated hyperswarmers tend to alternate fast and slow runs and have wider turning angles. Nonetheless, macroscopic measurement of swimming and swarming speed in colonies shows that hyperswarmers expand faster than wild-type on surfaces and through soft agar matrices. A mathematical model explains how wider turning angles lead to faster spreading when swimming through agar. Our study describes for the first time the swimming patterns in multiflagellated P. aeruginosa mutants and reveals that collective and individual motility in bacteria are not necessarily correlated. Understanding bacterial adaptations to surface motility, such as hyperswarming, requires a collective behavior approach.
Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo ...models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/β-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of β-catenin, preventing β-catenin from acting as a transcriptional co-activator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits β-catenin signalling, which then affects NC delamination.
It is known the interactions between the neural plate and epidermis generate neural crest (NC), but it is unknown why the NC develops only at the lateral border of the neural plate and not in the ...anterior fold. Using grafting experiments we show that there is a previously unidentified mechanism that precludes NC from the anterior region. We identify prechordal mesoderm as the tissue that inhibits NC in the anterior territory and show that the Wnt/β-catenin antagonist Dkk1, secreted by this tissue, is sufficient to mimic this NC inhibition. We show that Dkk1 is required for preventing the formation of NC in the anterior neural folds as loss-of-function experiments using a Dkk1 blocking antibody in Xenopus as well as the analysis of Dkk1-null mouse embryos transform the anterior neural fold into NC. This can be mimicked by Wnt/β-catenin signaling activation without affecting the anterior posterior patterning of the neural plate, or placodal specification. Finally, we show that the NC cells induced at the anterior neural fold are able to migrate and differentiate as normal NC. These results demonstrate that anterior regions of the embryo lack NC because of a mechanism, conserved from fish to mammals, that suppresses Wnt/β-catenin signaling via Dkk1.
Cancer cell collective migration is a complex behaviour leading to the invasion of cancer cells into surrounding tissue, often with the aid of stromal cells in the microenvironment, such as ...macrophages or fibroblasts. Although tumour–tumour and tumour–stromal intercellular signalling have been shown to contribute to cancer cell migration, we lack a fundamental theoretical understanding of how aggressive invasion emerges from the synergy between these mechanisms. We use a computational self-propelled particle model to simulate intercellular interactions between co-migrating tumour and stromal cells and study the emergence of collective movement. We find that tumour–stromal interaction increases the cohesion and persistence of migrating mixed tumour–stromal cell clusters in a noisy and unbounded environment, leading to increased cell cluster size and distance migrated by cancer cells. Although environmental constraints, such as vasculature or extracellular matrix, influence cancer migration in vivo, our model shows that cell–cell interactions are sufficient to generate cohesive and persistent movement. From our results, we conclude that inhibition of tumour–stromal intercellular signalling may present a viable therapeutic target for disrupting collective cancer cell migration.
Morphogenesis of the zebrafish neural tube requires the coordinated movement of many cells in both time and space. A good example of this is the movement of the cells in the zebrafish neural plate as ...they converge towards the dorsal midline before internalizing to form a neural keel. How these cells are regulated to ensure that they move together as a coherent tissue is unknown. Previous work in other systems has suggested that the underlying mesoderm may play a role in this process but this has not been shown directly in vivo.
Here we analyze the roles of subjacent mesoderm in the coordination of neural cell movements during convergence of the zebrafish neural plate and neural keel formation. Live imaging demonstrates that the normal highly coordinated movements of neural plate cells are lost in the absence of underlying mesoderm and the movements of internalization and neural tube formation are severely disrupted. Despite this, neuroepithelial polarity develops in the abnormal neural primordium but the resulting tissue architecture is very disorganized.
We show that the movements of cells in the zebrafish neural plate are highly coordinated during the convergence and internalization movements of neurulation. Our results demonstrate that the underlying mesoderm is required for these coordinated cell movements in the zebrafish neural plate in vivo.
Predicting evolution of expanding populations is critical to control biological threats such as invasive species and cancer metastasis. Expansion is primarily driven by reproduction and dispersal, ...but nature abounds with examples of evolution where organisms pay a reproductive cost to disperse faster. When does selection favor this 'survival of the fastest?' We searched for a simple rule, motivated by evolution experiments where swarming bacteria evolved into an hyperswarmer mutant which disperses \( \sim 100\%\) faster but pays a growth cost of \(\sim 10 \%\) to make many copies of its flagellum. We analyzed a two-species model based on the Fisher equation to explain this observation: the population expansion rate (\(v\)) results from an interplay of growth (\(r\)) and dispersal (\(D\)) and is independent of the carrying capacity: \(v=2\sqrt{rD}\). A mutant can take over the edge only if its expansion rate (\(v_2\)) exceeds the expansion rate of the established species (\(v_1\)); this simple condition (\(v_2 > v_1\)) determines the maximum cost in slower growth that a faster mutant can pay and still be able to take over. Numerical simulations and time-course experiments where we tracked evolution by imaging bacteria suggest that our findings are general: less favorable conditions delay but do not entirely prevent the success of the fastest. Thus, the expansion rate defines a traveling wave fitness, which could be combined with trade-offs to predict evolution of expanding populations.
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