Retinal development is impaired in <i>Crb1Crb2</i> cKO.

<p>(A–E) Histological sections from E13.5 to P5 control (left), <i>Crb1^+/−Crb2</i> cKO (middle) and <i>Crb1Crb2</i> cKO (right). From E13.5 onwards, disruption of the outer limiting membrane (A right, black arrowhead) accompanied with ectopic localization of cells extended in <i>Crb1Crb2</i> cKO developing retinas (A,B right). At E17.5 and P1, in contrast to control retinas no proper ganglion cell layer was formed (C,D). The separation of the outer nuclear/photoreceptor layer formed around P5, which never happened in the <i>Crb1Crb2</i> cKO retinas (E). <i>Crb1^+/−Crb2</i> cKO retinas showed the first disruption in the outer limiting membrane at the periphery at E15.5 (B middle, black arrowhead), which progressively extended to the centre accompanied with rosette formation (B–E middle). Electron microscopic pictures from E17.5 littermate control (F) and <i>Crb1Crb2</i> cKO (G) retinas. Control retinas showed an organized outer limiting membrane with adherens junctions (white arrowheads), retinal pigment epithelium and retinal nuclei alignments. <i>Crb1Crb2</i> cKO retinas showed absence of layer organization and adherens junctions. GCL, ganglion cell layer; INL, inner nuclear layer; NBL, neuroblast layer; ONL, outer nuclear layer; RPE, retinal pigmented epithelium. Scale bar, 100 µm (A–E); 5 µm (F,G).