Brain Organoids and the Study of Neurodevelopment

Abstract

Brain organoids are three-dimensional self-assembled structures composed of hundreds of thousands to millions of cells that resemble the cellular organization, transcriptional and epigenetic signature of a developing human brain. Advancements using brain organoids have been made to elucidate the genetic basis of certain neurodevelopmental disorders, such as microcephaly and autism; and to investigate the impact of environmental factors to the brain, such as during Zika infection. It remains to be explored how far brain organoids can functionally mature and process external information. An improved brain organoid model might reproduce important aspects of the human brain in a more reproducible and high-throughput fashion. This novel and complementary approach in the neuroscience toolbox opens perspectives to understand the fundamental features of the human neurodevelopment, with implications to personalize therapeutic opportunities for neurological disorders.

BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids

“…The rise of methods to generate pluripotent stem cell (PSC)-derived organoids containing multiple cellular subtypes arrayed in threedimensional (3D) structures has opened new avenues to decipher the principles underlying the emergence of patterns of differentiation (Huch et al, 2017;Trujillo and Muotri, 2018). These patterns are likely to be established in response to chemical and mechanical cues applied through culture medium and generated by the endogenous cellular diversity.…”

Progress of Induced Pluripotent Stem Cell Technologies to Understand Genetic Epilepsy

“…In the last three years, publications reporting the use of cerebral organoid raised exponentially. The cerebral organoids are 3D self-assembled structures obtained from human PSCs able to generate an organized architecture made of different kinds of cells and capable of functional behavior, recapitulating the human fetal brain [84][85][86].…”

The Mitotic Apparatus and Kinetochores in Microcephaly and Neurodevelopmental Diseases

“…On the other hand, centrosome and SAC-mutated drosophila strains are reported to be more tolerant to aneuploidy in the developing brain than in other epithelial tissues and respond to aneuploidy by lengthening the G1 phase of the cell cycle and undergoing premature differentiation [134,135]. These findings suggest a species-specific regulation of the response to chromosome missegregation in the developing brain [62] that requires being addressed with ad hoc experimental models [136,137].…”