Figure 8. From collective Integrin repression to Integrin activation and Fibronectin matrix fibrillogenesis.

(A–D) represent successive time points during somite border formation. Top images show tissue level changes in Fibronectin matrix while lower images show the underlying molecular processes at the cell membrane. (A) Within the unsegmented PSM, Integrin α5β1 is in the bent conformation and repression is maintained by physical interaction between Integrins on adjacent cells. Cdh2 promotes the association of Itgα5 on adjacent cell membranes and stabilizes the inactive Itgα5 conformation. Fibronectin dimers remain in soluble form in the extracellular space. This collective repression prevents FN fibrillogenesis internally within the tissue biasing fibrillogenesis to the tissue surface where collective repression is absent. (B) Cytoplasmic signals downstream of EphA4/Ephrinb2a, (light blue arrows) activate the Integrin heterodimer at the nascent somite border by inducing the extended conformation as well as Integrin clustering. Cdh2 levels diminish at the nascent boundary. (C) Activated Integrins bind soluble Fibronectin and assemble the dimers into an insoluble matrix. The Fibronectin matrix stabilizes Integrin clustering and induces Integrin signaling via Focal Adhesion Kinase (red). (D) Fibronectin matrix from the dorsal surface of the paraxial mesoderm involutes (yellow arrow) along the nascent border where it is integrated with the newly synthesized matrix to form a contiguous ECM between the tissue surface and the somite border.