The optic tectum is the major synaptic target of retinal axons in birds. In the chick, retinal ganglion cell axons enter the optic tectum through a superficial lamina (the stratum opticum), extended branches into deeper laminae, and arborize in specific "retinorecipient" laminae, where they form synapses. Studies using an organotypic culture system have provided evidence that the tectum bears a series of distinct, lamina-specific, cell surface-associated cues that direct these axonal behaviors (Yamagata and Sanes, 1995). Here, we have used a panel of antibodies to 30 membrane and matrix components to ask whether known adhesive molecules are distributed in lamina-specific patterns. Among many spatiotemporal pattern of expression documented, three were particularly noteworthy: (1) The cell adhesion molecules NgCAM/L1 and TAG-1/axonin-1 were concentrated in the stratum opticum. (2) SC1/JC7/DM-GRASP/BEN, N-cadherin, neuropilin, polysialylated N-CAM, and glycoconjugates recognized by the lectin VVA-B4 were concentrated in retinorecipient laminae. (3) Neurofascin, tenascin-C/cytotactin, and a matrix molecule defined by the "Sigma" antibody were present at highest levels in areas that border the retinorecipient laminae. Some members of each group (NgCAM/L1, TAG-1/axonin, SC1/JC7, polysialic acid, VVA-B4-receptors, and neurofascin) appeared on schedule and in lamina-restricted patterns in tecta from embryos that had been enucleated before retinal axons left the eye. Thus, molecules in these three categories could provide signals to retinal axons that promote extension through the stratum opticum, induce arborization or synaptogenesis in retinorecipient laminae, and prevent sprouting into adjoining laminae. Interestingly, N-cadherin accumulated in retinorecipient laminae only following the onset of synapse formation, and failed to accumulate in enucleated tecta. Immunoelectron microscopy of normal tecta demonstrated the presence of N-cadherin in the synaptic cleft, suggesting a role for this molecule in synaptic maintenance.

Processes of >100 types of interneurons (bipolar and amacrine cells) and projection neurons (retinal ganglion cells, RGCs) form specific and stereotyped patterns of connections in the inner plexiform layer (IPL) of the mouse retina. Four closely related homophilic immunoglobulin superfamily recognition molecules (Sidekick [Sdk] 1, Sdk 2, Dscam, and DscamL1) have been shown to play roles in patterning neuronal arbors and connections in chick retina, and all but Sdk1 have been shown to play related roles in mice. Here, we compare patterns of Sdk1 and Sdk2 expression in mouse retina and use genetic methods to assess roles of Sdk1. In adult retina, 3 neuronal types express sdk1 but not sdk2 at detectable levels, 5 express sdk2 but not sdk1 and 3 express both. Patterns of gene expression and protein localization at or near synapses are established during the first postnatal week. Dendrites of amacrine cells and RGCs that express sdk1 but not sdk2 arborize in the same narrow stratum in the center of the IPL. In the absence of Sdk1, this laminar restriction is degraded. Overexpression of sdk1 in developing cells that normally express sdk2 reorients their dendrites to resemble those of endogenously Sdk1-positive cells, indicating that Sdk1 plays an instructive role in patterning the IPL. Sdk1 fails to affect arbors when introduced after they are mature, suggesting that it is required to form but not maintain laminar restrictions. The effect of ectopically expressed sdk1 requires the presence of endogenous Sdk1, suggesting that the effect requires homophilic interactions among Sdk1-positive neurites. Together with previous results on Sdk2, Dscam, DscamL1, as well as the related Contactins, our results support the idea that an elaborate immunoglobulin superfamily code plays a prominent role in establishing neural circuits in the retina by means of tightly regulated cell type-specific expression and homophilically restricted intercellular interactions.

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