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eNeuro. 2018 Apr 26;5(2). pii: ENEURO.0368-17.2018. doi: 10.1523/ENEURO.0368-17.2018. eCollection 2018 Mar-Apr.

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

Author information

1
Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
2
Research Fellow of Japan Society for the Promotion of Science, Chiyoda, Tokyo 102-0083, Japan.
3
Department of Molecular Life Sciences, Tokai University School of Medicine, Isehara, 259-1193, Japan.
4
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
5
Department of Neurology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai 980-8574, Japan.
6
Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Bunkyoku, Tokyo 113-8421, Japan.

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.

KEYWORDS:

amyotrophic lateral sclerosis; areal patterning; fibroblast growth factor 8; pluripotent stem cell

PMID:
29707616
PMCID:
PMC5917473
DOI:
10.1523/ENEURO.0368-17.2018
[Indexed for MEDLINE]
Free PMC Article

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