Engineering human neuronal diversity: Morphogens and stem cell technologies for neurodevelopmental biology

A complex assortment of neuronal cells contributes to distinct functional circuits in the human brain. Such diversity is imposed upon pluripotent stem cells by a patterning process that begins much before the start of neurogenesis. Neural tube patterning relies on morphogens-diffusible signals that regulate transcription factor networks in progenitor cells, guiding spatial and temporal identity formation. Studying early human patterning in vivo is limited by access to embryonic tissue. Recent advances in stem cell technologies, including brain organoids, brain-on-chip systems, and assembloids, allow to explore morphogen-driven neurodevelopment. In this review, we highlight key mechanisms of neural tube patterning and how they enable insights into human brain development and neuropsychiatric disorders.