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Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina

Nature volume 451, pages 465–469 (2008)Cite this article

Abstract

Synaptic circuits in the retina transform visual input gathered by photoreceptors into messages that retinal ganglion cells (RGCs) send to the brain. Processes of retinal interneurons (amacrine and bipolar cells) form synapses on dendrites of RGCs in the inner plexiform layer (IPL). The IPL is divided into at least 10 parallel sublaminae; subsets of interneurons and RGCs arborize and form synapses in just one or a few of them1,2,3. These lamina-specific circuits determine the visual features to which RGC subtypes respond3,4,5. Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules—Dscam (Down’s syndrome cell adhesion molecule), DscamL (refs 6–9), Sidekick-1 and Sidekick-2 (ref. 10)—are expressed in chick by non-overlapping subsets of interneurons and RGCs that form synapses in distinct IPL sublaminae. Moreover, each protein is concentrated within the appropriate sublaminae and each mediates homophilic adhesion. Loss- and gain-of-function studies in vivo indicate that these IgSF members participate in determining the IPL sublaminae in which synaptic partners arborize and connect. Thus, vertebrate Dscams, like Drosophila Dscams11,12,13,14,15,16,17,18,19, play roles in neural connectivity. Together, our results on Dscams and Sidekicks suggest the existence of an IgSF code for laminar specificity in retina and, by implication, in other parts of the central nervous system.

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Figure 1: Expression and distribution of Dscams and Sidekicks in retina.
Figure 2: Dscams and Sidekicks mediate homophilic adhesion but do not adhere to each other.
Figure 3: Depletion of Dscam or Sidekick perturbs lamina-specific arborization.
Figure 4: Ectopic expression of Dscams or Sidekicks redirects lamina-specific arbors.

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Acknowledgements

We thank R. Burgess and colleagues for sharing data on mouse Dscam before submission, K. Hong for anti-sidekick-1 antiserum and M. J. Fraser (University of Notre Dame) for piggyBac plasmids. This work was supported by a grant from the NIH to J.R.S.

Author Contributions M.Y. and J.R.S. conceived the experiments. M.Y. performed the experiments. J.R.S. and M.Y. wrote the paper.

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  1. Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA,

    Masahito Yamagata & Joshua R. Sanes

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  1. Masahito Yamagata
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  2. Joshua R. Sanes
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Correspondence to Joshua R. Sanes.

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Yamagata, M., Sanes, J. Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina. Nature 451, 465–469 (2008). https://doi.org/10.1038/nature06469

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