Actualité - ASCB / EMBO

In the small intestine young cells compete to dislodge old cells

Valérie Devillaine
For an organism to function properly, cells must renew at a finely-tuned rate: neither too slow, nor too fast. Danijela Vignjevic’s team shed light on one of these mechanisms in the small intestine.
Denis - ASCB

A new intestine every seven days! The entire surface of our small intestine is replaced with a brand-new surface every week, making it the tissue with the fastest renewal rate. The ‘old’ cells on its surface continuously detach and are eliminated (known as cell extrusion), while under the surface, new cells are created to gradually replace the old ones (cell division). In order for the tissue to be renewed, the cells must continuously migrate from their division site to the extrusion area, while maintaining tissue integrity. How is this phenomenon regulated to avoid excess production or premature degeneration? To find out, Denis Krndija, a PhD studentfrom Danijela Vignjevic’s team, carried out genetic modifications on mice and developed a 3D imaging technique on live tissue.  In collaboration with Edouard Hannezo (Institute of Science and Technology (IST) in Austria), he developed a biophysical model to decrypt the mechanisms potentially involved in cell migration.

Scientists long believed that passive physical pressure applied by new cells emerging at the base of the intestine was responsible for pushing older cells ‘towards the exit’. But researchers demonstrated that this process only has a very limited impact. In reality, the trigger is an active phenomenon linked to Arp2/3 protein assembly that guides the new cells to the surface, causing the demise of older cells. More specifically, Arp2/3 proteins ensure protrusions are formed, outgrowths that allow cells to move around. Researchers were also able to measure the speed at which the phenomenon occurs, cell density and tissue tension, allowing them to quantify the balance needed between new and old cells to ensure an equilibrium in the system.