Sendai [Japan]December 25: Scientists from Tohoku University have, for the first time, provided experimental evidence that the viscosity of cells helps them stay ordered within the correct compartments during development. The way cells clump together, known as cell adhesion, appears to be enabled by a protein best known for its role in the immune system. The findings were detailed in the journal Nature Communications.
Scientists have long observed that unspecialized cells move in a way that ensures that cell groups destined for a specific tissue stick together. In 1964, American biologist Malcolm Steinberg proposed that cells with similar adhesiveness move to contact each other to minimize energy consumption, producing a thermodynamically stable structure. This is known as the differential adhesion hypothesis.
“Many other theoretical works have emphasized the importance of differences in cell-cell adhesion to separate cell populations and maintain boundaries between them, but this has not yet been demonstrated in the epithelial tissues of living animals,” says Erina Kuranaga of Tohoku University’s Laboratory for Histogenetic Dynamics, which led the investigation. “Our study showed, for the first time, that cell ordering is regulated by changes in adhesion.”
Kuranaga and his team conducted experiments on fruit fly pupae, finding that a gene, called Toll-1, played an important role in this adhesion process.
When fruit flies develop from the immature larval stage in the mature adult, the cells that form the epithelial tissue, called histoblasts, cluster into several “nests” in the abdomen. Each nest contains one front and one rear compartment. Histoblasts are meant to replace larval cells to form the adult epidermis, the outermost layer that covers flies. The cells in each compartment form distinct cell populations, so they must adhere together, with a distinct boundary forming between them.
Using fluorescent labels, Kuranaga and his team observed that the Toll-1 protein is mainly expressed in the posterior compartment. Its fluorescence also showed a sharp boundary between the two compartments.
Further investigation showed that Toll-1 performs the function of an adhesion molecule, encouraging similar cells to stick together. This process keeps the boundary between the two compartments straight, correcting the distortions that occur when cells divide to increase the number.
Interestingly, Toll proteins are best known for recognizing invading pathogens and little is known about their work beyond the immune system. “Our work improves understanding of the non-immune roles of Toll proteins,” Kuranaga says. She and her team plan to study the function of other Toll genes in fruit fly epithelial cells.
Proteins cause developing cells to come together
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