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The Journal of Neuroscience, November 15, 1998, 18(22):9409-9419

Membrane-Associated Molecules Guide Limbic and Nonlimbic Thalamocortical Projections

Fanny Mann¹, Victoria Zhukareva³, Aurea Pimenta², Pat Levitt², and Jürgen Bolz¹

¹ Institut National de la Santé et de la Recherche Médicale, Unité 371, Cerveau et Vision, 69500 Bron, France, ² Department of Neurobiology, University Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and ³ Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 15261

Membrane-associated signals expressed in restricted domains of the developing cerebral cortex may mediate axon target recognition during the establishment of thalamocortical projections, which form in a highly precise manner during development. To test this hypothesis, we first analyzed the outgrowth of thalamic explants from limbic and nonlimbic nuclei on membrane substrates prepared from limbic cortex and neocortex. The results show that different thalamic fiber populations are able to discriminate between membrane substrates prepared from target and nontarget cortical regions. A candidate molecule that could mediate selective choice in the thalamocortical system is the limbic system-associated membrane protein (LAMP), which is an early marker of cortical and subcortical limbic regions () that can promote outgrowth of limbic axons. Limbic thalamic and cortical axons showed preferences for recombinant LAMP (rLAMP) in a stripe assay. Incubation of cortical membranes with an antibody against LAMP prevented the ability of limbic thalamic fibers to distinguish between membranes from limbic cortex and neocortex. Strikingly, nonlimbic thalamic fibers also responded to LAMP, but in contrast to limbic thalamic fibers, rLAMP inhibited branch formation and acted as a repulsive axonal guidance signal for nonlimbic thalamic axons. The present studies indicate that LAMP fulfills a role as a selective guidance cue in the developing thalamocortical system.

Key words: wiring molecules; LAMP; cortical development; cortical areas; limbic system; thalamocortical projections; target recognition; axonal guidance

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18229409-11$05.00/0

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