Tohoku University scientists have, for the first time, provided experimental evidence that cell stickiness helps them stay sorted within correct compartments during development.
How tightly cells clump together, known as cell adhesion, appears to be enabled by a protein better known for its role in the immune system. The findings were detailed in the journal Nature Communications.
Scientists have long observed that not-yet-specialised cells move in a way that ensures that cell groups destined for a specific tissue stay together.
In 1964, American biologist Malcolm Steinberg proposed that cells with similar adhesiveness move to come in contact with each other to minimise energy use, producing a thermodynamically stable structure. This is known as the differential adhesion hypothesis.
Steinberg proposed that when cells form distinct tissues, specific cell-cell adhesion between cells from the same tissue can drive the separation. He further proposed that a difference in level of cell adhesion molecules expression between two cell types was sufficient to drive the separation.
Steinberg pioneered work in characterizing the physical properties of cells and tissues. He proposed that cell-cell adhesion drives tissue rounding up and, comparing tissues to liquids, he proposed that tissues have a surface tension. To measure tissue surface tension, he participated in building a compression device for rounded tissues.
“Many other theoretical works have emphasized the importance of differences in cell-to-cell adhesion for separating cell populations and maintaining the boundaries between them, but this had not yet been demonstrated in living animal epithelial tissues,” said Erina Kuranaga of Tohoku University’s Laboratory for Histogenetic Dynamics, who led the investigations. “Our study showed, for the first time, that cell sorting is regulated by changes in adhesion,” added Kuranaga.
Kuranaga and her team conducted experiments in fruit fly pupae, finding that a gene, called Toll-1, played a major role in this adhesion process.
As fruit flies develop from the immature larval stage into the mature adult, epithelial tissue-forming cells, called histoblasts, cluster together into several ‘nests’ in the abdomen. Each nest contains an anterior and a posterior compartment.
Histoblasts are destined to replace larval cells to form the adult epidermis, the outermost layer that covers the flies. The cells in each compartment form discrete cell populations, so they need to stick together, with a distinct boundary forming between them.
Using fluorescent tags, Kuranaga and her team observed the Toll-1 protein is expressed mainly in the posterior compartment. Its fluorescence also showed a sharp boundary between the two compartments.
Further investigations showed 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 distortions that arise as the 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,” said Kuranaga. She and her team next plan to study the function of other Toll genes in fruit fly epithelial cells. (ANI)
