Perturbation of the developing Xenopus retinotectal projection following injections of antibodies against beta1 integrin receptors and N-cadherin.

We have examined the function of beta1 integrin receptors and N-cadherin in the development of the Xenopus retinotectal projection. In vivo perturbation experiments were performed by injecting antibodies directed against beta1 integrin receptors and N-cadherin into the embryonic optic pathway. The antibodies were present during the initial development of the retinal projection, when the axons of the ganglion cells are migrating through the optic tract and terminating within the optic tectum. When injected individually, the antibodies were insufficient to cause obvious pathfinding errors. However, when injected together, the antibodies caused specific abnormalities in the development of the retinotectal projection. Pathfinding errors most commonly observed included ectopically projecting axons within the optic tract region, meandering and splaying of axons in the optic tectum, and the induction of prominent ipsilateral projections. IgGs and Fab' fragments of the antibodies produced pathfinding errors; these defects were not observed in animals injected with control antibodies. These in vivo results show that beta1 integrin receptors and N-cadherin have important roles during the development of the visual projection and provide evidence that a balance between cell-cell and cell-matrix adhesion may be critical for the normal development of the vertebrate visual system.