Defining stem cell states competent to self-organize morphogen signalling centres in human neural tube organoids

During development, groups of cells called 'organizers' release signals to induce pattern formation and morphogenesis in the surrounding tissues. This is crucial for formation of a coherent body plan. In the developing spinal cord, a key organizer is the floorplate, which secretes the morphogen Sonic Hedgehog to guide neuronal positioning along the ventral-dorsal axis. I will recapitulate this in vitro, harnessing stem cell self-organization properties to instate a floorplate in human neural tube organoids. I will use sophisticated microengineering technologies to recapitulate physiological microenvironments and impose conditions for reproducible organoid patterning. This will enable me to investigate the mechanistic link between early molecular events and subsequent floorplate self-organisation, with profound biomedical implications for engineering and regenerating patterned tissues with correct cell-type complexity and 3D architecture. This will provide a model for inaccessible stages of human nervous system development, and a source of functional human spinal cord for future biomedical applications.