Retinal tissue organization during early development: the role of apical and basal adhesive molecules.

The vertebrate neural retina is mainly composed of three cell layers separated by two synaptic layers. We have used the zebrafish embryo (Danio rerio) to characterize in detail the localization, polarization, and early differentiation of retinal ganglion cells (RGCs) and photoreceptors. Upon differentiation, both cell types exhibit a gradual transition from a neuroepithelial to a neuronal phenotype, which is stereotypical for each of them. However, RGCs are located basally and photoreceptors at the apical edge, so the processes occur with reverse orientations. Consistent with this, we found that RGCs depend on Laminin-α1 for positioning, while photoreceptors depend on N-Cadherin (Cdh2). 

More recent analyses of the effects of knockouts of the genes encoding these adhesive proteins have shown an important role for both molecules in the localization and orientation of other cells, as well as in the organization of retinal layers. We have found that reducing the expression of these proteins results in partial duplications of the neural retina, with particular characteristics for each situation. In the case of disruption of apical adhesion (both Cdh2 and Pals1/Nok), RGCs tend to accumulate at both retinal edges, while photoreceptors form rosettes distributed in the central region. Meanwhile, the functional elimination of Laminin1 causes RGCs to accumulate in the center of the retina, while photoreceptors are located on both surfaces. Particularly in this case, all layers are duplicated in an orderly manner, but in a mirror-image simmetry. 

By complementing these in vivo studies with the analysis of retinal organoids, we are able to discern the role of cell adhesion in the tissue organization of the retina during development.