THE LIMBIC SYSTEM-ASSOCIATED MEMBRANE-PROTEIN IS AN IG SUPERFAMILY MEMBER THAT MEDIATES SELECTIVE NEURONAL GROWTH AND AXON TARGETING

The formation of brain circuits requires molecular recognition between functionally related neurons. We report the cloning of a moleeule that participates in these interactions. The limbic system-associated membrane protein (LAMP) is an immunoglobulin (lg) superfamily member with 3 lg domains and a glycosyl-phosphatidylinositol anchor. In the developing forebrain, lamp is expressed mostly by neurons comprising limbic-associated cortical and subcortical regions that function in cognition, emotion, memory, and learning. The unique distribution of LAMP reflects its functional specificity. LAMP-transfected cells selectively facilitate neurite outgrowth of primary limbic neurons. Most striking, administration of anti-LAMP in vivo results in abnormal growth of the messy fiber projection from developing granule neurons in the dentate gyrus of the hippocampal formation, suggesting that LAMP is essential for proper targeting of this pathway. Rather than being a general guidance cue, LAMP likely serves as a recognition molecule for the formation of limbic connections.