Recapitulating cortical development with organoid culture <i>in vitro</i> and modeling abnormal spindle-like (ASPM related primary) microcephaly disease

doi:10.1007/s13238-017-0479-2

Protein Cell

2017, Vol. 8

Issue (11) : 823-833 https://doi.org/10.1007/s13238-017-0479-2

RESEARCH ARTICLE

Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease

Rui Li¹, Le Sun¹, Ai Fang^1,², Peng Li¹, Qian Wu^1,²(

), Xiaoqun Wang^1,^2,³(

)

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. University of Chinese Academy of Sciences, Beijing 100049, China
³. Beijing Institute for Brain Disorders, Beijing 100069, China

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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 theAspm 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.

Keywords neocortical development cerebral organoid microcephaly ASPM

Corresponding Author(s): Qian Wu,Xiaoqun Wang

Issue Date: 30 November 2017

Cite this article:

Rui Li,Le Sun,Ai Fang, et al. Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease[J]. Protein Cell, 2017, 8(11): 823-833.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-017-0479-2
https://academic.hep.com.cn/pac/EN/Y2017/V8/I11/823

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