The extracellular matrix (ECM) is a complex meshwork of proteins and proteoglycans that provides structure and support for cells and tissues. Cell migration needs formation and dissociation of cell-ECM linkages mainly formed by integrins. It was shown that increased ECM crosslinking favors migration of several cell types. We used the Drosophila eye disc to decipher the molecular network controling ECM crosslinking. During Drosophila eye development, glial cells migrate along a 400 nm thick ECM towards differentiating photoreceptor neurons. We stimulated glial motility by expression of activated PDGF-receptor (PVR) in Drosophila larvae and used atomic force microscopy (AFM) to explore the influence of lysyl oxidase (lox) and the integrin PS2 inflated on matrix crosslinking, represented here by elasticity. We found that downregualtion of lysyl oxidase (lox), a secreted protein, reduced the elasticity of ECM by 50%. Likewise, glial specific knockdown of integrin inflated also reduced ECM elasticity. Our data reveal a positive feedback loop ensuring a rigid ECM in the vicinity of migrating glial cells. Upon activation of PVR, expression of lox and integrin is activated. Lox is secreted and crosslinks extracellular matrix proteins to generate a more rigid ECM. The stiff ECM is recognized by integrin receptors and favors migration. Integrin signaling then promotes lox expression, which sustains ECM stiffness on the migratory path of the cell.

In conclusion, migrating glial cells not only adhere to the ECM via integrins, but in addition, integrin signaling actively modulates the ECM rigidity via a control of lox expression.