Setting Eyes on the Retinal Pigment Epithelium

Abstract

The neural component of the zebrafish eye derives from a small group of cells known as the eye/retinal field. These cells, positioned in the anterior neural plate, rearrange extensively and generate the optic vesicles (OVs). Each vesicle subsequently folds over itself to form the double-layered optic cup, from which the mature eye derives. During this transition, cells of the OV are progressively specified toward three different fates: the retinal pigment epithelium (RPE), the neural retina, and the optic stalk. Recent studies have shown that folding of the zebrafish OV into a cup is in part driven by basal constriction of the cells of the future neural retina. During folding, however, RPE cells undergo an even more dramatic shape conversion that seems to entail the acquisition of unique properties. How these changes occur and whether they contribute to optic cup formation is still poorly understood. Here we will review present knowledge on RPE morphogenesis and discuss potential mechanisms that may explain such transformation using examples taken from embryonic Drosophila tissues that undergo similar shape changes. We will also put forward a hypothesis for optic cup folding that considers an active contribution from the RPE.

Keywords: eye development; morphogenesis; optic cup; squamous epithelial cell; zebrafish (Danio rerio).

FIGURE 1

Schematic diagram of the time line of zebrafish eye morphogenesis. The top arrows (yellow to green) indicate the salient events in RPE development whereas bottom arrows (yellow to magenta) those related to the entire eye primordium. Eye structures are color coded: progenitors, light yellow; lateral/neural retina layer, dark pink; medial/RPE layer, green. BC, basal constriction; F, flattening; L, virtual lumen; LL, lateral layer; ML, medial layer; NR, neural retina; pNR, prospective neural retina; R, rim region; RM, rim movements; RPE, retinal pigment epithelium; pRPE, prospective RPE.

FIGURE 2

Diagrams comparing different mechanisms of epithelial flattening. (A) Left, the drawing depicts the immature Drosophila imaginal disk composed of a homogeneous layer of cuboidal cells (blue) and the mature disk composed of a columnar epithelium, the disk proper (pink) and a squamous layer, the peripodial epithelium (green). Right, the enlarged view depicts the differential microtubule (red lines and dots) organization of the two layers. (B) The left drawing depicts the development of the Drosophila egg chamber, which is surrounded by the follicular cells. The egg chamber is initially composed of a homogeneous cuboidal epithelium (blue) that then becomes flat in the anterior region (green) and columnar in the posterior one (pink). The right drawing depicts the contribution of Yorkie (Yki) to follicular cell flattening. (C) Schematic representation of the relation between sources of cell tension and YAP/TAZ cellular location (cytoplasmic vs. nuclear). (D) On the left, view of the Drosophila embryo at two different stages of development and relative cross sections showing the changes the amnioserosa undergoes (columnar in pink and squamous in green). The right panel depicts epithelial flattening of the amnioserosa cells driven by perpendicular rearrangement of the long axis of the cell (modified from Pope and Harris, 2008). (E) Left, view of two developmental stages of the Drosophila limb (the wing) and relative cross sections showing cell shape changes from columnar (pink) to cuboidal (blue). The right panel depicts ECM degradation and reorganization of myosin-II, which promote cell shortening. (F) Left, schematic representation of the zebrafish optic vesicle and optic cup, with the RPE in green, the neural retina in pink and the rim in blue. The right panel depicts two possible mechanisms that could contribute to RPE flattening, as discussed in the text. In all panels, arrowheads indicate mechanical forces; microtubules are represented in red, acto-myosin filaments in orange, ECM in brown and junctions in violet.