Functional roles of genetic risk factors for brain disorders in neurogenesis and neurodevelopment
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1.Building the brain from scratch:Engineering region-specific brain organoids from human stem cells to study neural development and disease
- 关键词：
- FAMILIAL ALZHEIMERS-DISEASE; MICROGLIA-LIKE CELLS; MAMMALIAN CORTICAL NEUROGENESIS; HUMAN CEREBRAL ORGANOIDS; ZIKA VIRUS-INFECTION; CHOROID-PLEXUS; DIRECTED DIFFERENTIATION; REGULATES NEUROGENESIS; FUNCTIONAL MATURATION; PARKINSONS-DISEASE
- Jacob, Fadi;Schnoll, Jordan G.;Song, Hongjun;Ming, Guo-li
- 《MOLECULAR MECHANISMS OF NEURAL DEVELOPMENT AND INSIGHTS INTO DISEASE》
- 2021年
- 会议
Human brain development is an intricate process that involves precisely timed coordination of cell proliferation, fate specification, neuronal differentiation, migration, and integration of diverse cell types. Understanding of these fundamental processes, however, has been largely constrained by limited access to fetal brain tissue and the inability to prospectively study neurodevelopment in humans at the molecular, cellular and system levels. Although non-human model organisms have provided important insights into mechanisms underlying brain development, these systems do not fully recapitulate many human-specific features that often relate to disease. To address these challenges, human brain organoids, self-assembled three-dimensional neural aggregates, have been engineered from human pluripotent stem cells to model the architecture and cellular diversity of the developing human brain. Recent advancements in neural induction and regional patterning using small molecules and growth factors have yielded protocols for generating brain organoids that recapitulate the structure and neuronal composition of distinct brain regions. Here, we first provide an overview of early mammalian brain development with an emphasis on molecular cues that guide region specification. We then focus on recent efforts in generating human brain organoids that model the development of specific brain regions and highlight endeavors to enhance the cellular complexity to better mimic the in vivo developing human brain. We also provide examples of how organoid models have enhanced our understanding of human neurological diseases and conclude by discussing limitations of brain organoids with our perspectives on future advancements to maximize their potential.
...2.Ontogeny of adult neural stem cells in the mammalian brain
- 关键词：
- RADIAL GLIAL-CELLS; OLFACTORY-BULB; DENTATE GYRUS; EMBRYONIC ORIGIN; SELF-RENEWAL; MOSAIC ORGANIZATION; PROGENITOR CELLS; EPENDYMAL CELLS; VASCULAR NICHE; CHOROID-PLEXUS
- Bond, Allison M.;Ming, Guo-Li;Song, Hongjun
- 《MOLECULAR MECHANISMS OF NEURAL DEVELOPMENT AND INSIGHTS INTO DISEASE》
- 2021年
- 会议
Neural stem cells (NSCs) persist into adulthood in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus and in the ventricular-subventricular zone (V-SVZ) of the lateral ventricles, where they generate new neurons and glia cells that contribute to neural plasticity. A better understanding of the developmental process that enables NSCs to persist beyond development will provide insight into factors that determine the size and properties of the adult NSC pool and thus the capacity for life-long neurogenesis in the adult mammalian brain. We review current knowledge regarding the developmental origins of adult NSCs and the developmental process by which embryonic NSCs transition into their adult form. We also discuss potential mechanisms that might regulate proper establishment of the adult NSC pool, and propose future directions of research that will be key to unraveling how NSCs transform to establish the adult NSC pool in the mammalian brain.
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