Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Ephrin-Eph signaling mediates the correct sorting of intestinal cells. Ephrins are a family of membrane-bound ligands that bind to the Eph family of tyrosine kinase receptors on adjacent cells.

In the intestinal crypt, Wnt signaling induces the expression of the EphB receptor in intestinal stem cells, ISCs, and Paneth cells and suppresses the expression of EphrinB ligands. 

As ISCs differentiate and move upward, the Wnt signaling weakens, which leads to a decrease in the expression of EphB and an increase in the production of EphrinB.

This causes the formation of the EphB-EphrinB gradient along the crypt-villus axis.  At the crypt-villi junction, EphrinB binds and activates the EphB expressed on the nearby cell through cell-cell contact.

This signaling pathway stimulates the degradation of cell adhesion proteins, leading to repulsion between EphB- and  Ephrin B-expressing cells.

Such repulsive events prevent the migration of EphB expressing ISCs and Paneth cells to the villi and separate them from the Ephrin B expressing differentiated cells.