Journal
ISCIENCE
Volume 23, Issue 6, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2020.101154
Keywords
-
Categories
Funding
- Research Council of Norway
- Regional Health Authority for South-Eastern Norway
- Novo Nordisk Foundation, Denmark
- University of Oslo, Norway
- European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) [609020]
- South East Regional Health Authority, Norway
- Faculty of Medicine and Health Sciences at NTNU
- Central Norway Regional Health Authority, Norway
- University of Turku, Finland
- Abo Akademi University, Finland
- Biocenter Finland, Finland
Ask authors/readers for more resources
Optic atrophy 1 (OPA1), a GTPase at the inner mitochondrial membrane involved in regulating mitochondrial fusion, stability, and energy output, is known to be crucial for neural development: Opa1 heterozygous mice show abnormal brain development, and inactivating mutations in OPA1 are linked to human neurological disorders. Here, we used genetically modified human embryonic and patient-derived induced pluripotent stem cells and reveal that OPA1 haploinsufficiency leads to aberrant nuclear DNA methylation and significantly alters the transcriptional circuitry in neural progenitor cells (NPCs). For instance, expression of the forkhead box G1 transcription factor, which is needed for GABAergic neuronal development, is repressed in OPA1+/- NPCs. Supporting this finding, OPA1+/- NPCs cannot give rise to GABAergic interneurons, whereas formation of glutamatergic neurons is not affected. Taken together, our data reveal that OPA1 controls nuclear DNA methylation and expression of key transcription factors needed for proper neural cell specification.
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