Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development
Abstract
In the human cerebral cortex, activities of excitatory neurons are balanced by local inhibition provided by cortical interneurons (cINs). Although disrupted cIN development contributes to neurodevelopmental disorders, molecular networks controlling this process were largely unknown. Here, we refined protocols for differentiating human embryonic stem cells into functional cINs. We defined gene-expression programs underlying cIN development and direct targets of the NKX2-1 transcription factor in this process, identifying potential regulators. These included CHD2, a gene mutated to cause human epilepsies. Accordingly, CHD2 deficiency impaired cIN development and altered later cIN function, while CHD2 and NKX2-1 could coregulate cIN gene expression by cobinding shared genomic regulatory regions. This work defines key features of both normal and disrupted cIN development.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2017
- DOI:
- 10.1073/pnas.1712365115
- Bibcode:
- 2017PNAS..11411180M