The E-cadherin cell cleanup mechanism has been identified by researchers working with live zebrafish and mouse embryos, showing that a protein long associated with holding epithelial tissues together also directs those tissues to engulf and remove nearby dead cells. The study, published in Nature Communications as article 8900 in volume 17, appeared on 27 August 2026, according to SciTechDaily.
E-cadherin is part of a molecular complex that connects the epithelial cells lining the skin, gut and airways. The complex includes three additional proteins. Together they give those tissue layers the structural strength to remain sealed. What the new research shows is that the same machinery can be repurposed: rather than simply connecting adjacent cells, it can gather at the point where a dying cell meets the tissue surface and orchestrate its removal.
What the experiments actually showed
The work was led by ICREA Research Professor Verena Ruprecht, with Hanna-Maria Häkkinen, Marta Batet Palau and Laura F. Bianchi as joint first authors. The team ran two key tests to determine whether E-cadherin on the dying cell itself was driving the response. First, they presented tissue with dying cells stripped of E-cadherin: the epithelial cells cleared those just as efficiently as normal dying cells. Second, they introduced fat droplets carrying no protein at all but displaying a surface signal associated with dying cells. The epithelial cells engulfed those droplets too.
The conclusion from both experiments is that E-cadherin on the dying cell is not what triggers the cleanup. The signal is something else, displayed on the dying cell’s surface, and the E-cadherin complex on the living epithelial cell is what responds to it.
‘We were intrigued to find out that epithelial cells repurpose their molecular adhesion machinery, the “glue” that normally holds them together, to engulf dying cells,’ Ruprecht said.
How the E-cadherin cell cleanup mechanism preserves the tissue barrier
Swallowing something roughly the size of a whole cell, while remaining part of a sealed protective barrier, is a considerable mechanical challenge. Live imaging resolved how the cells manage it. The upper and lower surfaces of a single epithelial cell behave independently during engulfment. The lower surface stretches and wraps around the dead material; the upper surface, which may face an external environment or an open lumen, remains comparatively unchanged. Measurements taken before, during and after the process showed very little change in the area of the upper surface, while the lower surface underwent substantial deformation.
Ruprecht described the behaviour as comparable to a row of dancers with linked arms: their upper bodies stay steady while their feet carry out increasingly complicated movements. ‘It’s the same dancer with a different choreography,’ she said.
Within the E-cadherin complex, individual proteins play distinct roles in this process. One acted as a tether, connecting the molecular assembly to the cell’s internal skeleton so that force could be transmitted across the surface of the material being engulfed. Cells lacking this protein, or lacking the specific region that attaches it to the skeleton, could no longer clear dead cells. A second component acted more like a brake on the cell’s contractile machinery. Removing that brake did not improve the cleanup: the cell became too stiff and lost its ability to remove dying cells at all.
The team also tested whether the mechanism extends beyond zebrafish. In early mouse embryos, blocking E-cadherin caused dying cells to remain uncleared, matching the zebrafish results. The researchers say this suggests the mechanism is shared among vertebrates.
The work builds on earlier research from Ruprecht showing that embryos use epithelial tissues to cooperatively remove dying cells, a behaviour the researchers describe as a form of early innate immune defence. Embryos are useful for this kind of investigation because they are transparent, allowing direct observation of living cells at a level of detail not currently achievable in adult human tissue, which the Centre for Genomic Regulation core facilities supported through advanced light microscopy.
An important limitation sits at the centre of the paper. Researchers do not yet know whether the same E-cadherin-dependent mechanism operates in adult zebrafish, adult mice, or any human tissue. Epithelial tissues in adults are already known to remove dying cells in places including the retina, colon, airways and mammary gland, and E-cadherin is present throughout adult epithelial tissue, so the researchers identify it as a plausible candidate for a more broadly used process. What they do not yet have is direct evidence that it functions this way in adult systems.
The potential relevance to human health rests on what happens when dead-cell clearance fails. Dying cells that are not removed can rupture and release their contents, contributing to chronic inflammation. Ruprecht described studying the mechanisms of efficient dead-cell removal as ‘of very high relevance to human health.’ The next step, unresolved in the published paper, is whether the same machinery is at work outside the embryo.
