RT Journal Article SR Electronic T1 Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0368-17.2018 DO 10.1523/ENEURO.0368-17.2018 A1 Kent Imaizumi A1 Koki Fujimori A1 Seiji Ishii A1 Asako Otomo A1 Yasushi Hosoi A1 Hiroaki Miyajima A1 Hitoshi Warita A1 Masashi Aoki A1 Shinji Hadano A1 Wado Akamatsu A1 Hideyuki Okano YR 2018 UL http://www.eneuro.org/content/early/2018/04/13/ENEURO.0368-17.2018.abstract AB 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.Significance Statement Although the cerebral cortex is organized into functionally unique subdivisions or areas, the areal specification has not been studied extensively in PSC-based neurodevelopmental models. Here, we report a culture system to control the areal identity of PSC-derived cerebral cortical progenitors along the R-C axis by modulating FGF8 signaling. Treatment with FGF8 conferred rostral (the sensorimotor cortex) identity on cerebral cortical progenitors, whereas these progenitors retained caudal (the temporal lobe) identity in the absence of FGF8. By using this culture system, we succeeded in modeling area-specific forebrain phenotypes (presumptive UMN phenotypes) of ALS. This system offers a novel platform in the field of human neurodevelopment and neurologic disease modeling.