scholarly journals Modeling the function of BAX and BAK in early human brain development using iPSC-derived systems

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Piyush Joshi ◽  
Caroline Bodnya ◽  
Megan L. Rasmussen ◽  
Alejandra I. Romero-Morales ◽  
Anna Bright ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Neural Development ◽  
Human Cancer ◽  
Model Systems ◽  
Mitochondrial Morphology ◽  
Double Knockout ◽  
Human Brain Development ◽  
Early Human

Abstract Intrinsic apoptosis relies on the ability of the BCL-2 family to induce the formation of pores on the outer mitochondrial membrane. Previous studies have shown that both BAX and BAK are essential during murine embryogenesis, and reports in human cancer cell lines identified non-canonical roles for BAX and BAK in mitochondrial fission during apoptosis. BAX and BAK function in human brain development remains elusive due to the lack of appropriate model systems. Here, we generated BAX/BAK double knockout human-induced pluripotent stem cells (hiPSCs), hiPSC-derived neural progenitor cells (hNPCs), neural rosettes, and cerebral organoids to uncover the effects of BAX and BAK deletion in an in vitro model of early human brain development. We found that BAX and BAK-deficient cells have abnormal mitochondrial morphology and give rise to aberrant cortical structures. We suggest crucial functions for BAX and BAK during human development, including maintenance of homeostatic mitochondrial morphology, which is crucial for proper development of progenitors and neurons of the cortex. Human pluripotent stem cell-derived systems can be useful platforms to reveal novel functions of the apoptotic machinery in neural development.

Human brain development and its in vitro recapitulation

2019 ◽  
Vol 138 ◽  
pp. 33-42 ◽  
Author(s):  
Yusuke Seto ◽  
Mototsugu Eiraku
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Human Brain Development

scholarly journals Challenges in Modeling Human Neural Circuit Formation via Brain Organoid Technology

2020 ◽  
Vol 14 ◽  
Author(s):  
Takeshi K. Matsui ◽  
Yuichiro Tsuru ◽  
Ken-ichiro Kuwako
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Neural Circuit ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Neural Lineage ◽  
Human Brain Development ◽  
Brain Organoid ◽  
Circuit Formation

Human brain organoids are three-dimensional self-organizing tissues induced from pluripotent cells that recapitulate some aspects of early development and some of the early structure of the human brain in vitro. Brain organoids consist of neural lineage cells, such as neural stem/precursor cells, neurons, astrocytes and oligodendrocytes. Additionally, brain organoids contain fluid-filled ventricle-like structures surrounded by a ventricular/subventricular (VZ/SVZ) zone-like layer of neural stem cells (NSCs). These NSCs give rise to neurons, which form multiple outer layers. Since these structures resemble some aspects of structural arrangements in the developing human brain, organoid technology has attracted great interest in the research fields of human brain development and disease modeling. Developmental brain disorders have been intensely studied through the use of human brain organoids. Relatively early steps in human brain development, such as differentiation and migration, have also been studied. However, research on neural circuit formation with brain organoids has just recently began. In this review, we summarize the current challenges in studying neural circuit formation with organoids and discuss future perspectives.

scholarly journals Unraveling Human Brain Development and Evolution Using Organoid Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Sarah Fernandes ◽  
Davis Klein ◽  
Maria C. Marchetto
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Brain Region ◽  
Model Systems ◽  
Transcriptional Signature ◽  
Human Brain Development ◽  
Advanced Stages ◽  
Brain Organoid ◽  
Development And Evolution ◽  
Human Specific

Brain organoids are proving to be physiologically relevant models for studying human brain development in terms of temporal transcriptional signature recapitulation, dynamic cytoarchitectural development, and functional electrophysiological maturation. Several studies have employed brain organoid technologies to elucidate human-specific processes of brain development, gene expression, and cellular maturation by comparing human-derived brain organoids to those of non-human primates (NHPs). Brain organoids have been established from a variety of NHP pluripotent stem cell (PSC) lines and many protocols are now available for generating brain organoids capable of reproducibly representing specific brain region identities. Innumerous combinations of brain region specific organoids derived from different human and NHP PSCs, with CRISPR-Cas9 gene editing techniques and strategies to promote advanced stages of maturation, will successfully establish complex brain model systems for the accurate representation and elucidation of human brain development. Identified human-specific processes of brain development are likely vulnerable to dysregulation and could result in the identification of therapeutic targets or disease prevention strategies. Here, we discuss the potential of brain organoids to successfully model human-specific processes of brain development and explore current strategies for pinpointing these differences.

scholarly journals Brain Organoids as Tools for Modeling Human Neurodevelopmental Disorders

Physiology ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 365-375 ◽  
Author(s):  
Jason W. Adams ◽  
Fernanda R. Cugola ◽  
Alysson R. Muotri
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Technological Advancement ◽  
Neurodevelopmental Disease ◽  
Human Brain Development ◽  
Therapeutic Development ◽  
Innovative Tool

Brain organoids recapitulate in vitro the specific stages of in vivo human brain development, thus offering an innovative tool by which to model human neurodevelopmental disease. We review here how brain organoids have been used to study neurodevelopmental disease and consider their potential for both technological advancement and therapeutic development.

scholarly journals Exploring early human brain development with structural and physiological neuroimaging

NeuroImage ◽  
2019 ◽  
Vol 187 ◽  
pp. 226-254 ◽  
Author(s):  
Lana Vasung ◽  
Esra Abaci Turk ◽  
Silvina L. Ferradal ◽  
Jason Sutin ◽  
Jeffrey N. Stout ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Early Human

scholarly journals Organoids: the third dimension of human brain development and disease

2021 ◽  
Author(s):  
Georgia Kouroupi ◽  
Kanella Prodromidou ◽  
Florentia Papastefanaki ◽  
Era Taoufik ◽  
Rebecca Matsas
Keyword(s):  
Stem Cells ◽  
Human Brain ◽  
Brain Development ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Two Dimensional ◽  
The Third ◽  
Human Brain Development ◽  
Third Dimension

Stem cell technologies have opened up new avenues in the study of human biology and disease. Especially, the advent of human embryonic stem cells followed by reprograming technologies for generation of induced pluripotent stem cells have instigated studies for modeling human brain development and disease by providing a means to simulate a human tissue with otherwise limited or no accessibility to researchers. Brain development is a complex process achieved in a remarkably controlled spatial and temporal manner through coordinated cellular and molecular events. In vitro models aim to mimic these processes and recapitulate brain organogenesis. Initially, two-dimensional neural cultures presented an innovative landmark for investigating human neuronal and, more recently, glial biology as well as for modeling brain neurodevelopmental and neurodegenerative diseases. The establishment of three-dimensional cultures in the form of brain organoids was an equally important milestone in the field. Brain organoids mimic more closely the in vivo tissue composition and architecture and are more physiologically relevant than monolayer cultures. They therefore represent a more realistic cellular environment for modeling the cell biology and pathology of the nervous system. Here we highlight the journey to recapitulate human brain development and disease in-a-dish, starting from two-dimensional in vitro systems up to the third dimension provided by brain organoids. We discuss the potential of these approaches for modeling human brain development and evolution and their promise for understanding and treating brain disease.

scholarly journals Brain anatomical networks in early human brain development

NeuroImage ◽  
2011 ◽  
Vol 54 (3) ◽  
pp. 1862-1871 ◽  
Author(s):  
Yong Fan ◽  
Feng Shi ◽  
Jeffrey Keith Smith ◽  
Weili Lin ◽  
John H. Gilmore ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Early Human
Sign in / Sign up

Export Citation Format

Share Document