ALCAM regulates mediolateral retinotopic mapping in the superior colliculus.
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. Because ALCAM has been suggested to interact with the IgSF adhesion molecule L1, a determinant of retinocollicular mapping, we hypothesized that ALCAM might direct topographic targeting to the superior colliculus (SC) by serving as a substrate within the SC for L1 on incoming retinal ganglion cell (RGC) axons. ALCAM was expressed in the SC during RGC axon targeting and on RGC axons as they formed the optic nerve; however, it was downregulated distally on RGC axons as they entered the SC. Axon tracing with DiI revealed pronounced mistargeting of RGC axons from the temporal retina half of ALCAM null mice to abnormally lateral sites in the contralateral SC, in which these axons formed multiple ectopic termination zones. ALCAM null mutant axons were specifically compromised 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-dependent attachment of acutely dissociated retinal cells and an L1-expressing, ALCAM-negative cell line, consistent with an ALCAM-L1 heterophilic molecular interaction. Together, these results suggest a model in which ALCAM in the SC interacts with L1 on RGC axons to promote medial extension of RGC axon branches important for mediolateral axon targeting in the formation of retinocollicular maps.
Buhusi
Mona
M
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
Demyanenko
Galina P
GP
Jannie
Karry M
KM
Dalal
Jasbir
J
Darnell
Eli P B
EP
Weiner
Joshua A
JA
Maness
Patricia F
PF
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping / Q000379:methods; D045744:Cell Line, Tumor; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism / Q000502:physiology; D012160:Retina / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D013477:Superior Colliculi / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology
D020410:Activated-Leukocyte Cell Adhesion Molecule; D039842:Neural Cell Adhesion Molecule L1