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J. Cell Biol., Volume 144, Number 2, January 25, 1999 339-349

Neurolin Ig Domain 2 Participates in Retinal Axon Guidance and Ig Domains 1 and 3 in Fasciculation

Christian A. Leppert, Heike Diekmann, Claudia Paul, Ute Laessing, Monika Marx, Martin Bastmeyer, and Claudia A.O. Stuermer

Department of Biology, University of Konstanz, D-78457 Konstanz, Germany

The optic disk-directed growth of retinal ganglion cell axons is markedly disturbed in the presence of polyclonal antineurolin antibodies, which mildly affect fasciculation (Ott, H., M. Bastmeyer, and C.A.O. Stuermer, 1998. J. Neurosci. 18:3363-3372).

New monoclonal antibodies (mAbs) against goldfish neurolin, an immunoglobulin (Ig) superfamily cell adhesion/recognition molecule with five Ig domains, were generated to assign function (guidance versus fasciculation) to specific Ig domains. By their ability or failure to recognize Chinese hamster ovary cells expressing recombinant neurolin with deletions of defined Ig domains, mAbs were identified as being directed against Ig domains 1, 2, or 3, respectively. Repeated intraocular injections of a mAb against Ig domain 2 disturb the disk-directed growth: axons grow in aberrant routes and fail to reach the optic disk, but remain fasciculated. mAbs against Ig domains 1 and 3 disturb the formation of tight fascicles.

mAb against Ig domain 2 significantly increases the incidence of growth cone departure from the disk-oriented fascicle track, while mAbs against Ig domains 1 and 3 do not. This was demonstrated by time-lapse videorecording of labeled growth cones.

Thus, Ig domain 2 of neurolin is apparently essential for growth cone guidance towards the disk, presumably by being part of a receptor (or complex) for an axon guidance component.

Key words: axon guidance;  receptor domain;  neurolin;  immunoglobulin superfamily;  retinal axons


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