Dorsal-ventral patterned neural cyst from human pluripotent stem cells in a neurogenic niche

Despite its importance in central nervous system development, development of the human neural tube (NT) remains poorly understood, given the challenges of studying human embryos, and the developmental divergence between humans and animal models. We report a human NT development model, in which NT-like tissues, neuroepithelial (NE) cysts, are generated in a bioengineered neurogenic environment through self-organization of human pluripotent stem cells (hPSCs). NE cysts correspond to the neural plate in the dorsal ectoderm and have a default dorsal identity. Dorsal-ventral (DV) patterning of NE cysts is achieved using retinoic acid and/or sonic hedgehog and features sequential emergence of the ventral floor plate, P3, and pMN domains in discrete, adjacent regions and a dorsal territory progressively restricted to the opposite dorsal pole. This hPSC-based, DV patterned NE cyst system will be useful for understanding the self-organizing principles that guide NT patterning and for investigations of neural development and neural disease.