Nat. Biotech. 37, 1198–1208 (2019).

As an early stage of human development, neurulation sees the formation of the main ectodermal lineages, including neural progenitors, neural crest, sensory placodes and epidermis. Ectodermal lineages are involved in a number of genetic diseases, underscoring the need for in vitro systems modeling the developmental processes involved. Haremaki et al. cultured pluripotent human embryonic stem cells (hESCs) on circular micropatterned substrates with dual-SMAD inhibition and subsequent BMP4 stimulation. The standardized neural structures generated (‘neuruloids’) are capable of self-organization and acquire fates representing the main lineages. Expression analysis of marker genes using single-cell RNA-sequencing data suggests neuruloids recapitulate development at the neural tube closure stages, from days 21 to 25. Applying this technology to generate neuruloids using isogenic Huntington’s disease hESCs, the authors identified disease-specific phenotypes manifesting during early development.