WASHINGTON, DC--Cell death is a fact of life for the developing embryo, as well as for thin protective barriers such as the lining of the gut. But how do the casualties get evacuated, and how do the tissues retain their integrity? Now scientists have found that dying cells signal their imminent demise and then get squeezed out by their neighbors, who make sure no gaps arise.
Throughout the body and in the growing embryo, cells are programmed to die. This happens through a process called apoptosis, which protects against diseases and sculpts developing tissues into the right shape. But apoptosis in an epithelium could potentially leave a gaping hole where the dying cell resided. To determine how organisms prevent this, cell biologist Jody Rosenblatt of the Medical Research Council Laboratory for Molecular Cell Biology at University College London and colleagues used a model epithelium in the laboratory.
To watch the cells die and disappear, the researchers, who reported their results 12 December at the American Society for Cell Biology meeting here, stained the DNA and cell membranes and exposed the cells to harmful ultraviolet radiation, forcing some cells to self-destruct. Suspicious that the proteins actin and myosin, which help cells move around and reshape themselves, were pushing the dead cells out of the epithelium, the scientists blocked the activities of both proteins. When healthy cells were deprived of the proteins, the apoptotic cells stayed put. This showed that, with actin and myosin, the neighbors were "squeezing out the dying cells like a tube of toothpaste," says Rosenblatt.
But when and where is the signal to produce extra actin and myosin coming from? Rosenblatt's team engineered a fluorescent version of actin so they could track its movement. The scientists then added healthy cells and others in various stages of apoptosis to the model epithelium. Only early apoptotic cells induced actin to form the contractile rings that pull in cell membranes away from their dying neighbor, squeezing it out.
"This is an important result," said cell biologist Jeffrey Settleman of Harvard Medical School in Boston. "The extrusion of apoptotic cells is fundamental in early embryonic development." Based on recent work in gut cells by other researchers, Rosenblatt also suspects this mechanism will be found in many simple epithelial systems.
Medical Research Council laboratory
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