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.

Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish

“…During optic cup morphogenesis, NR precursors retain this neuroepithelial morphology, whereas differentiating RPE cells undergo profound cell shape changes as they progressively flatten into a squamous epithelium (Moreno-Marmol, et al, 2018). These observations correlate in our analyses with a larger number of differentially upregulated genes and differentially opened chromatin regions at the RPE ( Figure S2).…”

“…Precursors at the LL elongate along their apico-basal axis, differentiate as NR, and constrict basally to direct the folding of the retinal neuroepithelium (Nicolas-Perez, et al, 2016;Ivanovitch, et al, 2013). In contrast, precursors at the ML either acquire a squamous epithelial shape and differentiate as RPE, or flow into the LL to contribute to the NR domain (Moreno-Marmol, et al, 2018;Sidhaye and Norden, 2017;Heermann, et al, 2015;Picker, et al, 2009).…”

Eye morphogenesis in the blind Mexican cavefish

“…Yet, the expansion and engulfment movement that this tissue is supposed to achieve to reach the rim of the retina and cover the whole retina is delayed compared to SF. In fact, this spreading and migration of RPE cells is concomitant with the rim movement and may contribute to it as a driving force (Cechmanek and McFarlane, 2017; Moreno-Marmol et al, 2018). This observation reinforces the idea that the rim movement is impaired in cavefish.…”

Stretching of the retinal pigment epithelium contributes to zebrafish optic cup morphogenesis

“…These progenitors are organized in a pseudostratified neuroepithelium, known as optic vesicle (OV) or eye primordium. In amniotes, the OVs appear as balloon structures positioned at the sides of the anterior neural tube (2). In zebrafish instead, these primordia are flat and form two bilayered structures with the outer and inner layers distally connected by a rim or hinge (3).…”