Journal article
Stem-cell derived neurosphere assay highlights the effects of viral infection on human cortical development
- Abstract:
-
Aberrant cortical development is a key feature of neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. Both genetic and environmental risk factors are thought to contribute to defects in cortical development; however, model systems that can capture the dynamic process of human cortical development are not well established. To address this challenge, we combined recent progress in induced pluripotent stem cell differentiation with advanced live cell imaging techniques to establish a novel three-dimensional neurosphere assay, amenable to genetic and environmental modifications, to investigate key aspects of human cortical development in real-time. For the first time, we demonstrate the ability to visualise and quantify radial glial extension and neural migration through live cell imaging. To show proof-of-concept, we used our neurosphere assay to study the effect of a simulated viral infection, a well-established environmental risk factor in neurodevelopmental disorders, on cortical development. This was achieved by exposing neurospheres to the viral mimic, polyinosinic:polycytidylic acid. The results showed significant reductions in radial glia growth and neural migration in three independent differentiations. Further, fixed imaging highlighted reductions in the HOPX-expressing outer radial glia scaffolding and a consequent decrease in the migration of CTIP2-expressing cortical cells. Overall, our results provide new insight into how infections may exert deleterious effects on the developing human cortex.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 9.3MB, Terms of use)
-
- Publisher copy:
- 10.1016/j.bbi.2023.11.017
Authors
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 203141/Z/16/Z
- 090532/Z/09/Z
- Funder identifier:
- https://ror.org/0187kwz08
- Grant:
- CL-2019-13-001
- Publisher:
- Elsevier
- Journal:
- Brain, Behavior, and Immunity More from this journal
- Volume:
- 115
- Pages:
- 718-726
- Publication date:
- 2023-11-22
- Acceptance date:
- 2023-11-16
- DOI:
- EISSN:
-
1090-2139
- ISSN:
-
0889-1591
- Pmid:
-
37995835
- Language:
-
English
- Keywords:
- Pubs id:
-
1573702
- Local pid:
-
pubs:1573702
- Deposit date:
-
2025-03-19
- ARK identifier:
Terms of use
- Copyright holder:
- Drydale et al.
- Copyright date:
- 2023
- Rights statement:
- © 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
If you are the owner of this record, you can report an update to it here: Report update to this record