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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\u20108 and N\u2010cadherin, influence the guidance and differentiation of hippocampal mossy fibers. Using organotypic hippocampal cultures, we find that cadherin\u20108 regulates mossy fiber fasciculation and targeting, but has little effect on CA3 dendrites. In contrast, N\u2010cadherin regulates mossy fiber fasciculation, but has little impact on axonal growth and targeting. However, N\u2010cadherin 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 \u03b2\u2010catenin in dentate gyrus (DG). This suggests that cadherins may engage different intracellular signaling cascades downstream of \u03b2\u2010catenin, coopt different extracellular binding partners, or target distinct subcellular domains. Together our findings demonstrate that cadherin\u20108 and N\u2010cadherin 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. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/hipo.20395","type":"journal-article","created":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T23:27:27Z","timestamp":1196983647000},"page":"349-363","source":"Crossref","is-referenced-by-count":75,"title":["Cadherin\u20108 and N\u2010cadherin differentially regulate pre\u2010 and postsynaptic development of the hippocampal mossy fiber pathway"],"prefix":"10.1002","volume":"18","author":[{"given":"Iddil H.","family":"Bekirov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Svoronos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George W.","family":"Huntley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna L.","family":"Benson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00317638"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901950106"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1523\/JNEUROSCI.23-30-09873.2003","article-title":"R\u2010cadherin is a Pax6\u2010regulated, growth\u2010promoting cue for pioneer axons","volume":"23","author":"Andrews GL","year":"2003","journal-title":"J Neurosci"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1016\/S0021-9258(19)39889-8","article-title":"N\u2010cadherin is stably associated with and is an acceptor for a cell surface N\u2010acetylgalactosaminylphosphotransferase","volume":"265","author":"Balsamo J","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_1_6_1","unstructured":"BekirovIH.2004.The role of classic cadherins in the development of hippocampal circuitry[Ph.D.]. 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