Extrinsic polarity cues control lamination versus cluster-based organization in vertebrate retinal development

A wide range of retinal architectures allow metazoans to sense and respond to their environment. Early eye anlagen in both invertebrates and vertebrates share an initial pseudo-stratified epithelial organization, which in vertebrates forms a laminated retina, whereas invertebrate neuroepithelia differentiate into repetitive clusters. The contribution of epithelial polarity to vertebrate retinal lamination has remained difficult to address in vivo. Using medaka (Oryzias latipes) retinal organoids, we modulated polarity to assess its impact on the retinal architecture. We show that organoids undergo a polarity-dependent morphological switch: continuous apico-basal cues promote the formation of laminated retinal epithelia, whereas their loss induces horizontally organized clusters of retinal cells constituting retinal columns. The addition of laminin restores lamination and switches the clustered architecture back to the familiar vertebrate organization. Our findings reveal unexpected plasticity in vertebrate retinal development and uncover an alternative mode of retinal patterning emerging in the absence of extrinsic polarity signals.