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Irina De la Huerta, Xin Duan, Masahito Yamagata, Joshua R Sanes; Expression and role of classical cadherins in the mammalian retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):714.
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The circuitry of the mammalian retina depends on the formation of correct synapses during development. Classical cadherins are homophilic adhesion molecules present at synapses in the central nervous system and known to stabilize neuronal contacts. In this study we describe the expression of classical cadherins in the mouse retina and examine the roles of selected cadherins in synaptic specificity.
In situ hybridization was used to determine the expression of 18 classical cadherins in the mouse retina during development. The cadherins that marked relatively small subsets of retinal ganglion cells (RGCs), or of bipolar or amacrine interneurons known to synapse with RGCs, were selected for further study. We used mouse lines in which a marker was knocked in after the start codon of each cadherin gene of interest to further characterize the connections made by cadherin-expressing neurons and to determine the effect of loss of cadherin expression.
We began by examining the expression of all classical cadherins in the mouse retina during development. Seven cadherins were expressed in RGCs and/or in bipolar and amacrine interneurons that are known to synapse with RGCs in the inner plexiform layer of the retina (IPL). The IPL is composed of 5 sublayers (S1-5), of which S1-3 are the OFF sublaminae while S4-5 are the ON sublaminae. We traced the projections of neurons expressing the seven cadherins of interest and determined that four cadherins (cdh 4, 8, 13, and 22) marked predominantly OFF-projecting RGCs while two cadherins (cdh 6 and 10) were expressed by ON-OFF RGCs. Cadherin 8 also marked a subset of OFF bipolar cells while cadherin 9 was expressed by a subset of ON bipolar cells. Analysis with previously validated markers showed that the cdh8- and cdh9-positive bipolar cells are types 2 and 5 respectively. Patterns of cadherin expression are established before eye opening and are therefore independent of visual experience. In ongoing work we are using loss- and gain-of-function studies to elucidate the roles of cdh8 and chd9 in the synaptic specificity of ON- and OFF- bipolar cells.
Classical cadherin expression distinguishes subtypes of RGCs and interneurons during development. Certain cadherins may play a role in targeting retinal interneurons to the appropriate synaptic sublaminae in the IPL.
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