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Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling.


ABSTRACT: 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.

SUBMITTER: Imaizumi K 

PROVIDER: S-EPMC5917473 | biostudies-literature | 2018 Mar-Apr

REPOSITORIES: biostudies-literature

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Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling.

Imaizumi Kent K   Fujimori Koki K   Ishii Seiji S   Otomo Asako A   Hosoi Yasushi Y   Miyajima Hiroaki H   Warita Hitoshi H   Aoki Masashi M   Hadano Shinji S   Akamatsu Wado W   Okano Hideyuki H  

eNeuro 20180301 2


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  ...[more]

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