Function of Neurolin and E587-Antigen during axonal pathfinding in the nervous system of gold- and zebrafish

Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) are involved in axon growth and fasciculation, and mediate essential functions as receptors or parts of receptor complexes during axon pathfinding. The aim of this work was to analyze the functions of the IgSF-CAMs Neurolin and E587-antigen in the nervous system of gold- and embryonic zebrafish. Blockage of Neurolin with polyclonal antibodies disturbs the pathfinding of young retinal ganglion cell (RGC) axons in the dorsal goldfish retina. These position specific defects suggests, that Neurolin functions as a receptor or part of a receptor complex for an axonal guidance component. Furthermore, Neurolin contributes slightly to the tight fasciculation of RGC axons. In contrast, blockage of E587-antigen through polyclonal antibodies causes a strong defasciculation of goldfish RGC axons, also most pronounced in the dorsal retina. E587-antigen is thus essentially involved in axon fasciculation and contributes to the creation of the age related order of RGC axons in the optic nerve. In embryonic zebrafish, blockage of E587-antigen disrupts the fasciculation of specific commissural and longitudinal axon trakts in the forebrain and hindbrain. Therefore E587-antigen is required for the creation of orderly axon projections along an axon-scaffold during the development of the zebrafish nervous system. Neurolin is only expressed on subsets of axons in embryonic zebrafish, e.g. the secondary motoraxons. Blockage of Neurolin causes pathfinding errors along all secondary motor axon projections, their delayed development and a less tight axon-association in fascicles. Thus, Neurolin is required for the directed growth and appropriate pathfinding decisions and most probably functions as a receptor for a guidance component in the path of secondary motor axons