The glue holding epithelial cells together also lets them swallow their dying neighbours

Epithelial cells seal the outer surface of an early embryo, and a protein complex best known for gluing them to one another turns out to be the tool they use to clear away neighbours that are dying. The adhesion machinery built around E-cadherin assembles at the contact point with a dying cell and helps the living cell wrap around it, all while the sheet stays watertight.

E-cadherin’s second job in clearing dying cells

The work comes from the lab of Verena Ruprecht, an ICREA research professor at the Centre for Genomic Regulation in Barcelona, and was published in Nature Communications on August 27, 2026, titled “De novo E-cadherin/catenin complex formation controls basal epithelial mechanics and force transmission for apoptotic cell clearance.” Hanna-Maria Häkkinen of the University of Innsbruck is listed as lead author, and News-Medical names Häkkinen, Marta Batet Palau and Laura F. Bianchi as joint first authors. The paper’s title puts the emphasis on mechanics, on how the basal side of the epithelium builds the complex and transmits force, rather than on chemical signalling alone, which is a different angle on the disposal of cells that die during development.

“Epithelial cells repurpose their molecular adhesion machinery, the glue that normally holds them together, to engulf dying cells,” Ruprecht said, as quoted by News-Medical. Two experiments in the group’s account show the mechanism does not depend on the dying cell carrying E-cadherin. Dead cells stripped of the protein were still removed effectively, and epithelial cells also engulfed fat droplets that carried dying-cell signals but no proteins.

A sealed top and a stretching base

The puzzle the team addressed is mechanical. An epithelium is a barrier, so a cell that opens itself to swallow a neighbour risks leaking. Live imaging showed the cells avoiding that by working the two faces independently: the basal surface, facing the embryo’s interior, stretches and deforms around the dead material, while the apical surface that faces outward stays stable and sealed.

The group describes this as asymmetrical reshaping, and it is how barrier integrity survives the clearance. The distinction matters because the same E-cadherin complex that must stay intact in the junctions between cells is being assembled anew at the point of contact with the dying cell, which is what the words “de novo” in the paper’s title refer to.

Alpha-catenin as the rope, p120-catenin as the brake

Two partner proteins in the complex do distinct work, per the AZoLifeSciences summary. One tethers the assembly to the cell’s skeleton and behaves like a rope that transmits force; the other acts as a brake on the cell’s contractile motor so the cell does not seize up. The Nature Communications paper names them: α-catenin links actin-generated forces to the target surface, letting engulfment progress without disrupting the junctions, and p120-catenin restrains myosin II at the contact site, preventing contraction strong enough to block clearance.

A December 2025 preprint of the work on bioRxiv adds numbers from the zebrafish experiments. Clearance efficiency fell from about 80 percent in controls to about 10 percent in embryos in which E-cadherin had been knocked down with morpholinos, and a blocking antibody against E-cadherin’s extracellular domain produced a similar defect. In the preprint, depleting α-catenin specifically impaired formation of the phagocytic cup while leaving the epithelial “arm” protrusions in place, and cells lacking the actin-binding domain of α-catenin cleared poorly. Knocking down p120-catenin caused myosin II to pile up and clearance to fail, a failure rescued with the myosin inhibitor blebbistatin. The preprint also reports smaller phagosomes in deficient conditions, and apoptotic targets that grew larger inside the embryo when clearance failed, a sign that the dying cells were not being taken up and broken down. These are preprint measurements, and the published paper’s figures may be framed differently.

Zebrafish and mouse embryos as test systems

The cells examined are specific. In zebrafish the team studied the enveloping layer, the epithelium that forms at the blastula stage and covers the embryo, across the stages from blastula to 70-80 percent epiboly. In mouse embryos they studied the trophectoderm, the outermost epithelium of the blastocyst, into whose cavity apoptotic mouse embryonic stem cells were injected. Blocking E-cadherin in the mouse embryos prevented clearance of the dying cells, which indicates the mechanism is conserved between a fish and a mammal. The preprint imaged the mouse embryos eight hours after the injection of dying cells.

No human tissue was examined. A later summary of the findings notes that uncleared debris contributes to chronic inflammation and that understanding efficient removal could point to targets in inflammatory diseases of epithelial tissues, but that is a stated motivation, not a result. The funders listed are the Spanish Ministry of Science and Innovation, the Human Frontier Science Program, the European Union’s Horizon Europe programme and the “la Caixa” Foundation.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.