Hayes, J.M., Hartsock, A., Clark, B.S., Napier, H.R., Link, B.A., and Gross, J.M. (2012) Integrin α5/fibronectin1 and focal adhesion kinase are required for lens fiber morphogenesis in zebrafish. Molecular biology of the cell. 23(24):4725-4738.
Lens fiber formation and morphogenesis requires a precise orchestration of cell-ECM and cell-cell adhesive changes in order
for a lens epithelial cell to adopt a lens fiber fate, morphology and migratory ability. The cell-ECM interactions that mediate
these processes are largely unknown, and here we demonstrate that Fn1, an ECM component, and integrin α5, its cellular binding
partner, are required in the zebrafish lens for fiber morphogenesis. Mutations compromising either of these proteins lead
to cataracts, characterized by defects in fiber adhesion, elongation and packing. Loss of integrin α5/Fn1 does not affect
the fate or viability of lens epithelial cells, nor does it affect the expression of differentiation markers expressed in
lens fibers, although nucleus degradation is compromised. Analysis of intracellular mediators of integrin α5/Fn1 activity,
FAK and ILK, revealed that FAK, but not ILK, is also required for lens fiber morphogenesis. These results support a model
in which lens fiber cells utilize integrin α5 to migrate along a FN-containing substrate on the apical side of the lens epithelium,
and on the posterior lens capsule, likely activating an intracellular signaling cascade mediated by FAK in order to orchestrate
the cytoskeletal changes in lens fibers that facilitate elongation, migration and compaction.