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

Photosensitive organs show remarkable structural diversity across the animal kingdom, ranging from vertebrate camera-type eyes to invertebrate compound eyes, despite deeply conserved gene regulatory networks controlling retinal development and identity. A shared feature of early retinal development is the formation of a polarized, pseudostratified neuroepithelium, which in vertebrates is maintained and elaborated into the laminated retina. How strongly this epithelial organization constrains retinal architecture, however, has remained difficult to address in vivo.

Using medaka retinal organoids, we modulated epithelial polarity and extracellular matrix support during retinal formation. Continuous polarity cues promoted the establishment of a laminated retinal neuroepithelium, whereas its absence caused a striking architectural switch. Instead of forming layers, differentiating retinal cell types self-organized in a non clonal way into regularly spaced horizontal clusters resembling invertebrate retinal units. Laminin supplementation efficiently rescued lamination.

Our findings reveal an unexpected structural plasticity of the vertebrate retina and demonstrate that tissue-level polarity cues are essential to stabilize laminar retinal organization. In their absence, retinal neurons adopt an alternative mode of self-organization, highlighting intrinsic patterning capacities that are normally masked by epithelial constraints.