Journal
ENEURO
Volume 5, Issue 2, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0368-17.2018
Keywords
amyotrophic lateral sclerosis; areal patterning; fibroblast growth factor 8; pluripotent stem cell
Categories
Funding
- New Energy and Industrial Technology Development Organization
- Ministry of Education, Science, Sports and Culture (MEXT) of Japan
- Ministry of Health, Labour and Welfare (MHLW) of Japan
- Program for Intractable Disease Research Utilizing Disease-Specific iPS Cells - Japan Science and Technology Agency (JST)/Japan Agency for Medical Research and Development (AMED)
- Practical Research Project for Rare/Intractable Diseases by AMED
- Ice Bucket Challenge Grant from Japan ALS Association
- Keio University Research Grants for Life Science and Medicine
- Grants-in-Aid for Scientific Research [17H06563] Funding Source: KAKEN
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The cerebral cortex is subdivided into distinct areas that have particular functions. The rostrocaudal (R-C) gradient of fibroblast growth factor 8 (FGF8) signaling defines this areal identity during neural development. In this study, we recapitulated cortical R-C patterning in human pluripotent stem cell (PSC) cultures. Modulation of FGF8 signaling appropriately regulated the R-C markers, and the patterns of global gene expression resembled those of the corresponding areas of human fetal brains. Furthermore, we demonstrated the utility of this culture system in modeling the area-specific forebrain phenotypes [presumptive upper motor neuron (UMN) phenotypes] of amyotrophic lateral sclerosis (ALS). We anticipate that our culture system will contribute to studies of human neurodevelopment and neurological disease modeling.
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