Cadherin-8 and N-cadherin differentially regulate pre- and postsynaptic development of the hippocampal mossy fiber pathway
Article first published online: 6 DEC 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 18, Issue 4, pages 349–363, April 2008
How to Cite
Bekirov, I. H., Nagy, V., Svoronos, A., Huntley, G. W. and Benson, D. L. (2008), Cadherin-8 and N-cadherin differentially regulate pre- and postsynaptic development of the hippocampal mossy fiber pathway. Hippocampus, 18: 349–363. doi: 10.1002/hipo.20395
- Issue published online: 17 MAR 2008
- Article first published online: 6 DEC 2007
- Manuscript Accepted: 30 OCT 2007
- NIDA. Grant Numbers: NS37731, NS34659, NS43083 (predoctoral training), MH075783, DA07135 (postdoctoral training)
- Irma T. Hirschl Career Scientist Award
- axon guidance;
- dendritic arborization;
Cells sort into regions and groups in part by their selective surface expression of particular classic cadherins during development. In the nervous system, cadherin-based sorting can define axon tracts, restrict axonal and dendritic arbors to particular regions or layers, and may encode certain aspects of synapse specificity. The underlying model has been that afferents and their targets hold in common the expression of a particular cadherin, thereby providing a recognition code of homophilic cadherin binding. However, most neurons express multiple cadherins, and it is not clear whether multiple cadherins all act similarly in shaping neural circuitry. Here we asked how two such cadherins, cadherin-8 and N-cadherin, influence the guidance and differentiation of hippocampal mossy fibers. Using organotypic hippocampal cultures, we find that cadherin-8 regulates mossy fiber fasciculation and targeting, but has little effect on CA3 dendrites. In contrast, N-cadherin regulates mossy fiber fasciculation, but has little impact on axonal growth and targeting. However, N-cadherin is essential for CA3 dendrite arborization. Both cadherins are required for formation of proper numbers of presynaptic terminals. Mechanistically, such differential actions of these two cadherins could, in theory, reflect coupling to distinct intracellular binding partners. However, we find that both cadherins bind β-catenin in dentate gyrus (DG). This suggests that cadherins may engage different intracellular signaling cascades downstream of β-catenin, coopt different extracellular binding partners, or target distinct subcellular domains. Together our findings demonstrate that cadherin-8 and N-cadherin are critical for generating the mossy fiber pathway, but that each contributes differentially to afferent and target differentiation, thereby complementing one another in the assembly of a synaptic circuit. © 2007 Wiley-Liss, Inc.