Cell-surface molecules play an essential role in guiding axons to their targets. We have developed a method to generate monoclonal antibodies (MAbs) which recognize cell-surface molecules of defined molecular weight that are expressed during the development of the chicken retinotectal system. The antigen distribution on optic fibers recognized by one of these MAbs, Bravo, is restricted to retinal ganglion cell axons in the retina, and absent from these same axons in the tectum.
The complete derived sequence of Bravo including four putative alternatively spliced regions has been obtained. It reveals a close relationship to the neural members of the immunoglobulin superfamily, with closest relationship to chicken Ng-CAM and mouse L1. Like Ng-CAM and L1, Bravo contains six immunoglobulin domains, five fibronectin type III repeats, a transmembrane domain and a highly conserved but functionally uncharacterized cytoplasmic region. Like the other neural members of the immunoglobulin superfamily, Bravo carries the HNK-1 carbohydrate epitope, and specifically like L1 and Ng-CAM, Bravo is found predominantly in the form of a heterodimer, an intact chain cleaved in identical locations in all three molecules into two non-covalently associating parts.
These data present an interesting view of retinotectal optic fiber outgrowth: As optic fibers grow in dense fascicles towards the optic nerve exit, they express both the known cell adhesion molecule Ng-CAM, and the closely related Bravo. As these fibers pass through the optic chiasm, Bravo is reduced on their surfaces, coincidentally in the same place and time that these fibers noticeably defasciculate, presumably to allow independent target seeking by individual axons.
Furthermore, Bravo staining of retinal glial processes has been detected. The close relationhip of Bravo to Ng-CAM coupled to Ng-CAM's known homophilic binding capacity suggest Bravo may be the heterophilic glial ligand for Ng-CAM long postulated to exist. Bravo is identical in sequence with the recently characterized Ng-CAM related glycoprotein, Nr-CAM
