Abstract
The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.
Highlights
The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease
While animal models have long served as tools to uncover human neurobiology, their limitations have continued to emphasize the need for a reliable human model system where species-specific developmental trajectories and healthy and disease pathophysiology can be convincingly captured
The basal ganglia arise from the ventral telencephalon, an anterior extension of ventral neuraxis, which is patterned by the sonic hedgehog (SHH) signaling pathway in normal vertebrate development
Summary
The development of the human central nervous system (CNS) is a complex series of sequential molecular events that guide cellular proliferation, differentiation, and migratory patterns to build the organization of what are the most advanced neural circuits in the animal kingdom. From a simple non-invasive skin biopsy [10], or more recently urine [21,22] or blood samples [23,24,25], the patient’s cells are reprogrammed into iPSCs and cultured to become neural organoids while maintaining the subject’s specific genetic background. This individualized nature carries the potential to reveal brain cytoarchitecture that resembles that of the person from whom the cells originally came. Given that the organoids capture embryonicand fetal-stage development best, deciphering whether organoids are applicable to both neurodevelopmental and neurodegenerative disorders is an ongoing investigation
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call