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Malformations of Human Neocortex in Development - Their Progenitor Cell Basis and Experimental Model Systems
Anneline Pinson1, Takashi Namba1, Wieland B Huttner1
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Frontiers in Cellular Neuroscience
|July 25, 2019
Summary
Human neocortex malformations, including microcephaly and macrocephaly, are linked to neural stem/progenitor cell (NPC) dysfunction. This review examines NPC biology and evaluates model systems for studying these developmental brain disorders.
Area of Science:
- Developmental neuroscience
- Genetics
- Cell biology
Background:
- Neocortical malformations cause intellectual disability, epilepsy, and autism.
- Genomic advances reveal molecular bases for these disorders.
- Focus on microcephaly and macrocephaly linked to neural stem/progenitor cells (NPCs).
Purpose of the Study:
- Review NPC cell biology and markers in neocortical malformations.
- Evaluate experimental models for studying these developmental disorders.
- Highlight limitations of mouse models and emerging alternatives.
Main Methods:
- Literature review of genetic and genomic studies.
- Analysis of NPC biology and markers.
- Comparative assessment of experimental model systems (mice, ferrets, primates, organoids).
Main Results:
- NPCs are central to microcephaly and macrocephaly.
- Mouse models have limitations due to interspecies differences in NPC types and proliferation.
- Ferrets, non-human primates, and cerebral organoids offer valuable alternatives.
Conclusions:
- Understanding NPC biology is crucial for neocortical malformation research.
- Interspecies differences necessitate diverse model systems.
- Cerebral organoids and other non-murine models enhance the study of human neocortical development and disease.
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