Synergistic neurite-outgrowth promoting activity of two related axonal proteins, Bravo/Nr-CAM and G4/Ng-CAM in chicken retinal explants.

In the developing chicken retina, optic fibres migrating to the tectum express on their surfaces several cell adhesion molecules, including Bravo/Nr-CAM and G4/Nr-CAM and G4/Ng-CAM. We have previously described differential distribution along the retinotectal projection and differential modulation by environmental cues for Bravo and G4 and here we further compare the characteristics of these immunoglobulin superfamily molecules. From day 6 of embryonic development (E6) to 20 (E20), Bravo and G4 were found to coexist in the retinal optic fibre layer. However, while G4 staining was confined to that layer, as development proceeded Bravo staining spread to plexiform layers and some radial structures of the retina. G4 displayed a dose-dependent neurite-outgrowth promoting activity for E6 retinal explants, while Bravo did not support neurite growth. Surprisingly, when the retinal explants were grown on mixtures of the two molecules, a much more vigorous growth of neurites was seen, revealing a synergistic effect. We propose that Bravo and G4, as well as other axonal surface molecules, affect axonal growth in different ways when they are present in combination than when they are alone.