Mona Buhusi,1Galina P. Demyanenko,1 Karry M. Jannie,2 Jasbir Dalal,1 Eli P. B. Darnell,1 Joshua A. Weiner,2 and Patricia F. Maness1
1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, and 2Department of Biology, University of Iowa, Iowa City, Iowa 52242
ALCAM [activated leukocyte cell adhesion molecule (BEN/SC-1/DM-GRASP)]is a transmembrane recognition molecule of the Ig superfamily(IgSF) containing five Ig domains (two V-type, three C2-type).Although broadly expressed in the nervous and immune systems,few of its developmental functions have been elucidated. BecauseALCAM has been suggested to interact with the IgSF adhesionmolecule L1, a determinant of retinocollicular mapping, we hypothesizedthat ALCAM might direct topographic targeting to the superiorcolliculus (SC) by serving as a substrate within the SC forL1 on incoming retinal ganglion cell (RGC) axons. ALCAM wasexpressed in the SC during RGC axon targeting and on RGC axonsas they formed the optic nerve; however, it was downregulateddistally on RGC axons as they entered the SC. Axon tracing withDiI revealed pronounced mistargeting of RGC axons from the temporalretina half of ALCAM null mice to abnormally lateral sites inthe contralateral SC, in which these axons formed multiple ectopictermination zones. ALCAM null mutant axons were specificallycompromised in medial orientation of interstitial branches,which is known to require the ankyrin binding function of L1.As a substrate, ALCAM–Fc protein promoted L1-dependentattachment of acutely dissociated retinal cells and an L1-expressing,ALCAM-negative cell line, consistent with an ALCAM–L1heterophilic molecular interaction. Together, these resultssuggest a model in which ALCAM in the SC interacts with L1 onRGC axons to promote medial extension of RGC axon branches importantfor mediolateral axon targeting in the formation of retinocollicularmaps.