Nok plays an essential role in maintaining the integrity of the outer nuclear layer in the zebrafish retina

Abstract

Proper visual function of the vertebrate retina requires the maintenance of the integrity of the retinal outer nuclear layer (ONL), which is often affected in many blinding human retinal diseases.While the structural integrity of the ONL has long been considered to be maintained primarily through the outer limiting membrane (OLM), we have little knowledge on the development and maintenance of the OLM itself. Here, by analyzing the adhering properties of photoreceptors in zebrafish N-cad and nok mutants, we demonstrated for the first time that the nok gene is essential for the establishment and/or maintenance of the OLM. In addition, our results imply the possibility that Nok, Crumbs, and their associated proteins may constitute a type of photoreceptor-photoreceptor junctional complex that has not been described before. Thus, our study provides novel insights into the mechanisms by which the integrity of the ONL is maintained in the vertebrate retina.

Unraveling the Genetic Complexity of Drosophila stardust During Photoreceptor Morphogenesis and Prevention of Light-Induced Degeneration

“…In the zebrafish Danio rerio, mutations in the crb ortholog oko meduzy result in defects in apico-basal polarity of the neuroepithelium, and inactivation of its paralogs crb2b or crb3a affects the differentiation of apical characteristics of PRCs and renal cells (Malicki and Driever 1999;Omori and Malicki 2006). The zebrafish sdt ortholog nagie oko is essential for the cellular patterning of the retina (Wei and Malicki 2002;Wei et al 2006). These results suggest that this protein complex serves conserved functions during cell polarization in different species.…”

The Crumbs complex: from epithelial-cell polarity to retinal degeneration

“…Mutations in the zebrafish sdt orthologue nagie oko prevent the establishment and maintenance of the OLM, and disrupt the layering of the retina (Wei and Malicki, 2002;Wei et al, 2006a). In the mammalian retina, MPP5 colocalises with LIN-7C, MUPP1 [also known as multiple PDZ domain protein (MPD)] and PATJ in the subapical region, apical to the OLM (Stöhr et al, 2005;van de Pavert et al, 2004).…”

“…Mice lacking all three genes die around birth without major defects in external tissue morphogenesis, but with deficiencies in breathing and in synaptic transmission (Jo et al, 1999;Irie et al, 1999) MALS-3 (VELI-3) colocalises in the mouse retina with MPP5 in the outer limiting membrane, and with MPP4, another MAGUK protein, in the outer plexiform layer Expressed in the kidney on the the basolateral membrane of cells of the collecting duct, and on the basolateral membrane and the tight junction in proximal tubule cells MALS-3 single-knockout mice exhibit regional defects in epithelial polarisation in the kidney, associated with disruption of tight junctions and development of cystic and fibrotic tissue Knockdown of MALS-3 in epithelial cells in culture impairs tight-junction formation and destabilises Pals1 and PATJ (Stöhr et al, 2005) ) (Olsen et al, 2005) (Straight et al, 2006) (Olsen et al, 2007) Zebrafish lin7 -1, lin7-2, lin7-3 Localisation apical to the adherens junctions in neuroepithelial cells depends on Nagie oko; expressed in various layers of the mature retina (Wei et al, 2006a) MALS, mammalian LIN-7; VELI, vertebrate homolog of LIN-7. (Malicki and Driever, 1999;Omori and Malicki, 2006) in cells in the pronephric duct, and knockdown of crb3a leads to length reduction of the auditory kinocilia in cells of the inner ear (Omori and Malicki, 2006).…”

Multiple domains of Stardust differentially mediate localisation of the Crumbs-Stardust complex during photoreceptor development inDrosophila

“…In addition, mutations in human CRB1 are associated with Retinitis pigmentosa 12 (RP12) and Leber congenital amaurosis (LCA) (reviewed in Assémat et al, 2008;Richard et al, 2006b). Mutation of crb and sdt orthologues in the zebrafish (Danio rerio) (oko meduzy and nagie oko, respectively) affects cellular patterning of the retina and apical membrane differentiation of some cell types, including the PRC (Malicki and Driever, 1999;Omori and Malicki, 2006;Wei and Malicki, 2002;Wei et al, 2006). Thus, the Crb-Sdt complex performs conserved functions during cell polarisation and retinal morphogenesis in different species.…”