Abstract
In Dictyostelium discoideum, a model organism for the study of collective cell migration, extracellular cyclic adenosine 3’,5’-monophosphate (cAMP) acts as a diffusible chemical guidance cue for cell aggregation, which has been thought to be important in multicellular morphogenesis. Here we revealed that the dynamics of cAMP-mediated signaling showed a transition from propagating waves to steady state during cell development. Live-cell imaging of cytosolic cAMP levels revealed that their oscillation and propagation in cell populations were obvious for cell aggregation and mound formation stages, but they gradually disappeared when multicellular slugs started to migrate. A similar transition of signaling dynamics occurred with phosphatidylinositol 3,4,5-trisphosphate signaling, which is upstream of the cAMP signal pathway. This transition was programmed with concomitant developmental progression. We propose a new model in which cAMP oscillation and propagation between cells, which are important at the unicellular stage, are unessential for collective cell migration at the multicellular stage.
Highlights
In Dictyostelium discoideum, a model organism for the study of collective cell migration, extracellular cyclic adenosine 3’,5’-monophosphate acts as a diffusible chemical guidance cue for cell aggregation, which has been thought to be important in multicellular morphogenesis
In spite of these traditional views of cAMP relay for the coordination of collective cell migration in Dictyostelium, some observations suggest that the role of cAMP relay in slugs is controversial. acaA-null cells, which lack the ability of cAMP relay, normally cannot aggregate and form multicellular bodies, but the phenotypes of the mutant are rescued by constitutive activation of PKA, which is downstream of the cAMP signaling pathway, implying that Dictyostelium cells have developmental ability without cAMP oscillation[19]
We investigated the dynamics of cAMP signals through the development of Dictyostelium cells by visualizing the changes in cytosolic cAMP levels ([cAMP]i), which reflect the response to cAMP relay
Summary
In Dictyostelium discoideum, a model organism for the study of collective cell migration, extracellular cyclic adenosine 3’,5’-monophosphate (cAMP) acts as a diffusible chemical guidance cue for cell aggregation, which has been thought to be important in multicellular morphogenesis. Live-cell imaging of cytosolic cAMP levels revealed that their oscillation and propagation in cell populations were obvious for cell aggregation and mound formation stages, but they gradually disappeared when multicellular slugs started to migrate. We found that [cAMP]i oscillation and its propagation, which is an index of cAMP relay, gradually decreased and disappeared after slug formation This result indicates a dramatic transition of cAMP signaling dynamics during the development of Dictyostelium cells and the possibility that oscillatory cAMP signaling is not essential for collective cell migration in slugs, which challenges the traditional view about the role of cAMP relay in the organization of collective cell migration
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