Visualizing a traveling wave of cell death

Apoptosis propagates through the cytoplasm as trigger waves.

When diffusion is too slow for communication over long distances, cells can use waves of chemical activity. By using fluorescent probes and microscopy, Cheng and Ferrell show that in frog eggs (which are very large cells), waves of apoptotic signals can be seen passing through the egg cytoplasm. The pathways that trigger cell death have positive feedback loops that lead to self-regenerating waves. The speed of the waves (∼30 micrometers per minute) is too fast to be explained by diffusion.

Apoptosis is an evolutionarily conserved form of programmed cell death critical for development and tissue homeostasis in animals. The apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves. We tested this possibility in cell-free Xenopus laevis egg extracts and observed apoptotic trigger waves with speeds of ~30 micrometers per minute. Fractionation and inhibitor studies implicated multiple feedback loops in generating the waves. Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers per minute, which were tightly correlated with caspase activation. Thus, apoptosis spreads through trigger waves in both extracts and intact cells. Our findings show how apoptosis can spread over large distances within a cell and emphasize the general importance of trigger waves in cell signaling.

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