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

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 in vivo 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. Total RNA from human ES cell-derived control neurospheres (n=3) and FGF8-treated neurospheres (n=3) was analyzed.