Purchase this article with an account.
Peter G Fuerst; Differential Cell Adhesion in Organization of the Cone Synapse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):715.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Development of the retina’s functional circuitry involves the coordinated interactions of multiple cell types. Despite the limited number of cell types in the retina compared to other parts of the brain the retina contains some of the nervous system’s most complex synapses. For example, development of cone synapses involves multiple bipolar and horizontal cells contacting and making synapses with distinct cone photoreceptors, each of which in turn is contacted by multiple bipolar cells of different types.
In this study we assay the localization of cadherin, protocadherin and IGF superfamily adhesion molecules, as well as PDZ containing scaffolding molecules and catenins at the cone synapse. Functional analysis of these molecules was focused on gain and loss of function of the IGF superfamily gene Dscam (Down Syndrome Cell Adhesion Molecule). The influence of cell density, cell death and disorganization of downstream circuitry was also assayed by utilizing bax, bcl2 and cleaved caspase 3 null mice and by conditional disorganization of inner retinal circuitry. The integrity of the cone synapse was assayed by immunohistochemistry, 3-dimensional electron microscopy and electroretinography (ERG) analysis.
A complex localization pattern of cell adhesion molecules was observed. For example some bipolar cells make contacts at both cone and rod synapses and localization of some cadherins was observed on the bipolar cell dendrites contacting cone but not rod synapses. Functional analysis of Dscam function in the outer plexiform layer indicated that this gene is required to provide heteroneuronal recognition within cell types, while ectopic expression resulted in the formation of ectopic synapses in the outer nuclear and photoreceptor layers. A role for cell density and the integrity of downstream circuitry was found with respect to the contacts between some bipolar cells and the cone synapse.
Our data are consistent with the differential adhesion hypothesis of development. As more players underlying adhesion-mediated organization of the retina are discovered an elegant picture of the mechanism underlying retinal synaptic organization is emerging.
This PDF is available to Subscribers Only