Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease.
10.1007/s13238-017-0479-2
- Author:
Rui LI
1
;
Le SUN
1
;
Ai FANG
1
;
Peng LI
1
;
Qian WU
2
;
Xiaoqun WANG
3
Author Information
1. State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. qianwu@ibp.ac.cn.
3. State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. xiaoqunwang@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
ASPM;
cerebral organoid;
microcephaly;
neocortical development
- MeSH:
Action Potentials;
physiology;
Biomarkers;
metabolism;
Cell Culture Techniques;
Embryoid Bodies;
cytology;
metabolism;
Gene Expression;
Humans;
Induced Pluripotent Stem Cells;
cytology;
metabolism;
Lateral Ventricles;
cytology;
growth & development;
metabolism;
Microcephaly;
genetics;
metabolism;
pathology;
Models, Biological;
Mutation;
Neocortex;
cytology;
growth & development;
metabolism;
Nerve Tissue Proteins;
deficiency;
genetics;
Neurogenesis;
genetics;
Neurons;
cytology;
metabolism;
Organoids;
cytology;
metabolism;
PAX6 Transcription Factor;
genetics;
metabolism;
Patch-Clamp Techniques;
SOXB1 Transcription Factors;
genetics;
metabolism;
Zonula Occludens-1 Protein;
genetics;
metabolism
- From:
Protein & Cell
2017;8(11):823-833
- CountryChina
- Language:English
-
Abstract:
The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.
