Journal
NATURE
Volume 545, Issue 7652, Pages 54-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature22330
Keywords
-
Categories
Funding
- NIH/National Institute of Mental Health (NIMH) [R01MH100900, R01MH100900-02S1]
- NIMH BRAINS Award [R01MH107800]
- California Institute of Regenerative Medicine (CIRM)
- MQ Fellow Award
- Donald E. and Delia B. Baxter Foundation
- Kwan Research Fund
- Stanford Start-up Funds
- Child Research Health Institute (CHRI)
- Walter V. and Idun Berry Postdoctoral Fellowship
- Stanford Medicine Dean's Fellowship
- American Epilepsy Society
- Wishes for Elliott Foundation
- NIH [5P01HG00020526]
- UCSF Program for Breakthrough Biomedical Research
- Sandler Foundation
Ask authors/readers for more resources
The development of the nervous system involves a coordinated succession of events including the migration of GABAergic (gamma-aminobutyric-acid-releasing) neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here we generate three-dimensional spheroids from human pluripotent stem cells that resemble either the dorsal or ventral forebrain and contain cortical glutamatergic or GABAergic neurons. These subdomain-specific forebrain spheroids can be assembled in vitro to recapitulate the saltatory migration of interneurons observed in the fetal forebrain. Using this system, we find that in Timothy syndrome-a neurodevelopmental disorder that is caused by mutations in the Ca(V)1.2 calcium channel-interneurons display abnormal migratory saltations. We also show that after migration, interneurons functionally integrate with glutamatergic neurons to form a microphysiological system. We anticipate that this approach will be useful for studying neural development and disease, and for deriving spheroids that resemble other brain regions to assemble circuits in vitro.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available