Abstract
Propagating waves of cAMP, periodically initiated in the aggregation centre, are known to guide the chemotactic aggregation of hundreds of thousands of starving individual Dictyostelium discoideum cells into multicellular aggregates. Propagating optical density waves, reflecting cell periodic movement, have previously been shown to exist in streaming aggregates, mounds and migrating slugs. Using a highly sensitive cAMP-FRET reporter, we have now been able to measure periodically propagating cAMP waves directly in these multicellular structures. In slugs cAMP waves are periodically initiated in the tip and propagate backward through the prespore zone. Altered cAMP signalling dynamics in mutants with developmental defects strongly support a key functional role for cAMP waves in multicellular Dictyostelium morphogenesis. These findings thus show that propagating cAMP not only control the initial aggregation process but continue to be the long range cell-cell communication mechanism guiding cell movement during multicellular Dictyostelium morphogenesis at the mound and slugs stages.
Highlights
Propagating waves of cAMP, periodically initiated in the aggregation centre, are known to guide the chemotactic aggregation of hundreds of thousands of starving individual Dictyostelium discoideum cells into multicellular aggregates
Variations in initial cell density, amplified by the increase in cell density during the first few waves of aggregation, lead to the formation of bifurcating aggregation streams, a phenomenon known as a streaming instability3. cAMP waves primarily propagate through these streams from the aggregation centre outward, directing the collective cell movement of highly polarised cells, towards the aggregation centre resulting in the formation of the mound
Extracellular cAMP is detected via G protein coupled cAMP receptors, upon stimulation of the receptors this results in a signal transduction chain that leads to the activation of two processes, activation of a specific transmembrane adenylyl cyclase (AcA) that produces cAMP and a slower adaptation process that results in inhibition of cyclase activation[8]
Summary
Propagating waves of cAMP, periodically initiated in the aggregation centre, are known to guide the chemotactic aggregation of hundreds of thousands of starving individual Dictyostelium discoideum cells into multicellular aggregates. Altered cAMP signalling dynamics in mutants with developmental defects strongly support a key functional role for cAMP waves in multicellular Dictyostelium morphogenesis These findings show that propagating cAMP control the initial aggregation process but continue to be the long range cell-cell communication mechanism guiding cell movement during multicellular Dictyostelium morphogenesis at the mound and slugs stages. Experiments with a temperature sensitive acaA construct have shown that optical density waves in aggregates and mounds as well as slug migration are dependent on active AcA24 This suggests that this adenylyl cyclase continues to produce cAMP signals in mound and slug stages guiding chemotactic movement of cells in these stages of development. Measurement of aberrant cAMP signalling dynamics in three mutants, the aggregation stage adenylyl cyclase AcA, the internal phosphodiesterase RegA and the cell contact molecules TgrB1 and TgrC1, all with defects in multicellular development, strongly support a functional role for cAMP propagation in multicellular Dictyostelium development
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