Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids

Summary The development of the visual system involves the coordination of spatial and temporal events to specify the organization of varied cell types, including the elongation of axons from retinal ganglion cells (RGCs) to post-synaptic targets in the brain. Retinal organoids recapitulate many features of retinal development, yet have lacked downstream targets into which RGC axons extend, limiting the ability to model projections of the human visual system. To address these issues, retinal organoids were generated and organized into an in vitro assembloid model of the visual system with cortical and thalamic organoids. RGCs responded to environmental cues and extended axons deep into assembloids, modeling the projections of the visual system. In addition, RGC survival was enhanced in long-term assembloids, overcoming prior limitations of retinal organoids in which RGCs are lost. Overall, these approaches will facilitate studies of human visual system development, as well as diseases or injuries to this critical pathway.
Graphical abstract
Highlights • Human stem cell-derived RGC axons respond to target-derived cues • Assembloids were generated between retinal, thalamic, and cortical organoids • Retinofugal projections robustly extend toward thalamic targets
In this article, Fligor and colleagues present the development of a three-dimensional assembloid model for retinofugal projections, comprising retinal, thalamic, and cortical organoids. Results presented include a detailed analysis of enhanced RGC survival and robust axonal outgrowth and provide the opportunity to explore methods for RGC regeneration and disease modeling.