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Peter Fuerst, Shuai Li, Dee Schramm; Synaptic localization but not specificity is mediated by Down Syndrome Cell Adhesion Molecule. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4567.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Development of the vertebrate retina involves the generation of several classes of cells and their subsequent organization into functioning circuits. Experimental evidence indicates that organization of neural circuits is mediated in part by differential expression of cell adhesion molecules in different cell types. The combination of adhesion molecules a given cell expresses than guides the formation of appropriate cellular spacing and connectivity. In this study we assay the function of the gene Down Syndrome Cell Adhesion Molecule (Dscam) in the formation of retinal circuitry.
Methods: Gain and loss of function transgenic mice were developed and verified and used alongside newly developed antibody reagents and in vivo transfection to map the localization and function of DSCAM during development of the mouse retina.
Results: DSCAM protein was found to be excluded from the active zone of synapses in the inner plexiform layer and localized to the perisynaptic region of the cone bipolar cell synapse in the outer plexiform layer. The effect of Dscam deletion and over-expression or ectopic expression was assayed on synapse distribution. A dramatic reorganization of horizontal cell, bipolar cell and photoreceptor synaptic lamination was observed as the result of ectopic expression.
Conclusions: Dscam appears to primarily play a role in organizing cells of a given type within a cell type. The lack of DSCAM immunoreactivity at synapse active zones suggests the protein may play more of a role in the placement of synapses than specifying connectivity between cell types. Despite the lack of DSCAM at synapses, its ability to redirect synaptic lamination suggests that it is acting to guide dendrite lamination, and we are currently assaying the degree to which this can be explained by adhesion, promoting synaptic localization, or repulsion, excluding synapse formation at certain locations. Over-expression of Dscam also resulted in an increase in developmental cell death, consistent with the decrease in developmental cell death observed in Dscam mutant mice. Together, these results illustrate the role of adhesion molecules in development of retinal architecture and how organization of cell circuits and synaptic lamination can be mediated.
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