Purpose: In invertebrates such as Drosophila melanogaster and Caenorhabditis elegans, the PDZ domain containing proteins, Discs large (Dlg) and Scribble (Scrib), are found localized to specific junctional complexes and have been shown to be required for establishing and maintaining epithelial cell adhesion, polarity, and proliferation during development. In addition, they are known to be critical for neural development. However, the mechanisms and pathways through which they act in mammalian systems, especially in vivo, are poorly understood. The purpose of this study was to characterize the distribution of Dlg-1 and Scrib in various structures of the mouse eye and the regions where these proteins overlap with known adhesion proteins.
Methods: Embryos or mouse eyes were embedded, sectioned, subjected to immunofluorescence with antibodies to Dlg-1, Scrib, and E-cadherin, N-cadherin, or ZO-1, and stained sections viewed under confocal microscopy.
Results: Dlg-1 and Scrib were found widely distributed throughout the eye. In the lens, overlap was observed with E- and N-cadherin and ZO-1 in regions where adherens junctions are found, as well as in the complexes that attach lens cells to the underlying capsule. Overlap of Dlg-1 and Scrib with E-cadherin and ZO-1 was observed in the portions of the cornea and in the retinal pigment epithelium. However, in the neural retina, there appeared to be little, if any, overlap of Dlg-1 or Scrib with adhesion proteins, consistent with a role in synapse biology in the neural retina rather than adhesion.
Conclusions: The observed localization of Dlg-1 and Scrib with cadherins suggests that these proteins may play roles in cell adhesion, polarity and proliferation, as they do in invertebrates, suggesting cross-species conservation of function for these PDZ proteins. However, the broader distribution of these PDZ proteins within the eye suggests they may play more diverse roles in cell adhesion and differentiation.