ABOVE: Fruit fly epithelial cells (pseudo colored in this micrograph) work together during development to ensure that even when cells die, gaps don’t form in the tissue.


The paper
L. Valon et al., “Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination,” Dev Cell
doi:10.1016/j.devcel.2021.05.006, 2021.

As the body’s first line of defense against microbial intruders, epithelial cells are known for their ability to form tight physical and chemical barriers in tissues. But just how they maintain these barriers, often only a single cell layer thick, continues to intrigue researchers. Romain Levayer, a cell and developmental biologist at the Institut Pasteur in France, and his colleagues were particularly interested in how epithelial cells are able to balance their plasticity and high turnover with maintaining a robust barrier. After all, says Levayer, “if you have a gap . . . you can’t control what comes in and what comes out.” 

The group found that when epithelial cells die inside developing fruit flies (Drosophila melanogaster), they rarely die in clusters—rather, the dead cells seem to be spread throughout the tissue. To determine why, the researchers created transgenic fruit flies with cells whose death could be triggered by blue light, giving the researchers exquisite control over each cell’s fate. They found that when they killed clusters of three or more cells, it impaired the epithelium’s ability to seal itself off, compared with when the cells were killed in a single-file line. 

The team also found that the tissue’s natural sparse distribution of dying cells seems to be mediated by bursts of ERK signaling between dying cells and healthy ones nearby. ERK is involved in regulating the cell cycle, gene expression, and cell survival, among other things. In this instance, ERK signaling prevented cells from sharing the same fate as their apoptotic neighbors, a mechanism that was recently discovered in human cells too. Levayer likens this kind of local self-organizing to a string quartet, where musicians receive their cues by listening to one another, rather than an orchestra that is led by a conductor. “In the end,” he says, “you end up having something well-organized at the tissue level.”

“I thought it was very cool work,” says Zara Weinberg, a cell biologist at the University of California, San Francisco, who was not involved with the study. “The degree to which they carefully mapped out the spatial organization of cell death did not leave me with a lot of concerns about the phenotype that they were observing,” she says, noting that their analysis was “very powerful.”