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Updated: Dec 13, 2025
Electroporation of Sliced Human Cortical Organoids for Studies of Gene Function
Published on: November 29, 2024
Cerebral organoids to unravel the mechanisms underlying malformations of human cortical development
Olivia Krefft1, Philipp Koch1, Julia Ladewig1
1Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, Mannheim, Germany; Hector Institute for Translational Brain Research (HITBR gGmbH), Mannheim, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract:
Genetic studies identified multiple mutations associated with malformations of cortical development (MCD) in humans. When analyzing the underlying mechanisms in non-human experimental models it became increasingly evident, that these mutations accumulate in genes, which functions evolutionary progressed from rodents to humans resulting in an incomplete reflection of the molecular and cellular alterations in these models. Human brain organoids derived from human pluripotent stem cells resemble early aspects of human brain development to a remarkable extent making them an attractive model to investigate MCD. Here we review how human brain organoids enable the generation of fundamental new insight about the underlying pathomechanisms of MCD. We show how phenotypic features of these diseases are reflected in human brain organoids and discuss challenges and future considerations but also limitations for the use of human brain organoids to model human brain development and associated disorders.
Insights
Human brain organoids offer a powerful model for studying malformations of cortical development (MCD). These organoids accurately reflect human brain development, providing new insights into disease mechanisms.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Genetic mutations are linked to human malformations of cortical development (MCD).
- Existing animal models incompletely replicate human MCD mechanisms due to evolutionary gene divergence.
- Human brain organoids derived from pluripotent stem cells offer a promising alternative model.
Purpose of the Study:
- To review the utility of human brain organoids in understanding MCD.
- To highlight how organoids model human brain development and associated disorders.
- To discuss the challenges and limitations of using organoids for MCD research.
Main Methods:
- Review of current literature on human brain organoids and MCD.
- Analysis of how organoid models reflect human developmental processes.
- Examination of phenotypic features of MCD in organoid systems.
Main Results:
- Human brain organoids effectively model early human brain development.
- Organoids recapitulate key molecular and cellular alterations seen in human MCD.
- Phenotypic disease features are observable in these organoid models.
Conclusions:
- Human brain organoids provide crucial insights into MCD pathomechanisms.
- Organoids represent a significant advancement for studying human neurodevelopmental disorders.
- Further research is needed to address challenges and limitations for comprehensive modeling.
