Crb Apical Polarity Proteins Maintain Zebrafish Retinal Cone Mosaics via Intercellular Binding of Their Extracellular Domains

Abstract

Cone photoreceptors are assembled by unknown mechanisms into geometrically regular mosaics in many vertebrate species. The formation and maintenance of photoreceptor mosaics are speculated to require differential cell-cell adhesion. However, the molecular basis for this theory has yet to be identified. The retina and many other tissues express Crumbs (Crb) polarity proteins. The functions of the extracellular domains of Crb proteins remain to be understood. Here we report cell-type specific expression of the crb2a and crb2b genes at the cell membranes of photoreceptor inner segments and Müller cell apical processes in the zebrafish retina. We demonstrate that the extracellular domains of Crb2a and Crb2b mediate a cell-cell adhesion function, which plays an essential role in maintaining the integrity of photoreceptor layer and cone mosaics. Because Crb proteins are expressed in many types of epithelia, the Crb-based cell-cell adhesion may underlie cellular patterning in other epithelium-derived tissues as well.

Drosophila Crumbs prevents ectopic Notch activation in developing wings by inhibiting ligand-independent endocytosis

“…It was reported to modify ligand-dependent Notch activity (Herranz et al, 2006;Richardson and Pichaud, 2010), and to mediate nonautonomous effects on cell survival (Hafezi et al, 2012). Other results suggested that the extracellular domain is engaged in homophilic interactions to stabilise Crb in the membrane, both in the Drosophila follicular epithelium (Fletcher et al, 2012) and in the zebrafish retina (Zou et al, 2012).…”

A functional role of the extracellular domain of Crumbs in cell architecture and apicobasal polarity

“…Based on indirect data some reports suggested the ability of Crb molecules to interact with other Crb molecules (Chen et al, 2010;Fletcher et al, 2012;Pellikka et al, 2002;Wei et al, 2006) or other proteins (Herranz et al, 2006;Richardson and Pichaud, 2010). Moreover, a recent study describes adhesion between zebrafish Crb molecules (Zou et al, 2012).…”

AP-2-complex-mediated endocytosis of Drosophila Crumbs regulates polarity by antagonizing Stardust

“…A positive-feedback loop through homophilic interactions between extracellular domains of Crb in cis has been suggested to keep Crb on the apical membrane of follicle cells and thus ensures polarity (Fletcher et al, 2012). In addition, homophilic interactions in trans between the extracellular domains of Crb molecules on neighboring cells have been proposed to contribute to Crb stabilization on the apical membrane, both in Drosophila (Letizia et al, 2013;Röper, 2012) and in zebrafish (Zou et al, 2012).…”