A unique membrane protein is expressed on early developing limbic system axons and cortical targets

Abstract

The limbic system-associated membrane protein (LAMP) is a 64 kDa protein that, in the adult brain, is present in cortical and subcortical regions comprising the limbic system (Levitt, 1984). The developmental expression of LAMP was studied in fetal rat brains to determine the specific patterns of distribution and the cellular elements that exhibit LAMP immunoreactivity. Light microscopic immunocytochemical analysis revealed that LAMP is expressed on neurons and their growing axons early in fetal development, at a time coincident with pathway formation and differentiation of limbic system nuclei. In the forebrain, where limbic system structures are heavily concentrated, immunoreactivity appears on subpopulations of axons in a temporal sequence that correlates with the time of formation of pathways carrying limbic system axons. Thus, staining is evident first at embryonic day (E) 15 on fibers within the internal capsule coursing from the diencephalon to cortex. LAMP immunoreactivity appears over the next 3 d in the anterior commisure, fornix, and corpus callosum. Ultrastructural immunocytochemical analysis reveals dense surface staining of fascicles of developing axons and growth cones. The axonal staining is transient, disappearing during the second postnatal week of development. In cerebral cortex, cells in presumptive limbic cortical regions such as lateral perirhinal sulcal cortex and prefrontal cortex are LAMP immunoreactivity from the inception of the cortical plate. These cortical regions are clearly delineated from surrounding unstained nonlimbic areas as early as E15. Thus, LAMP expression in the cortex may represent one of the earliest markers of specific cytoarchitectonic areas. The early, stereotyped pattern of LAMP expression in subpopulations of developing axons and limbic regions, combined with our recent functional studies (Keller and Levitt, 1987), suggests that this unique cell-surface protein may be an important element in linking different components of a functional system in the mammalian brain.