FGF-MAPK signaling regulates human deep-layer corticogenesis
AuthorGantner, CW; Hunt, CPJ; Niclis, JC; Penna, V; McDougall, SJ; Thompson, LH; Parish, CL
Source TitleStem Cell Reports
AffiliationFlorey Department of Neuroscience and Mental Health
Anatomy and Neuroscience
Document TypeJournal Article
CitationsGantner, C. W., Hunt, C. P. J., Niclis, J. C., Penna, V., McDougall, S. J., Thompson, L. H. & Parish, C. L. (2021). FGF-MAPK signaling regulates human deep-layer corticogenesis. STEM CELL REPORTS, 16 (5), pp.1262-1275. https://doi.org/10.1016/j.stemcr.2021.03.014.
Access StatusOpen Access
Despite heterogeneity across the six layers of the mammalian cortex, all excitatory neurons are generated from a single founder population of neuroepithelial stem cells. However, how these progenitors alter their layer competence over time remains unknown. Here, we used human embryonic stem cell-derived cortical progenitors to examine the role of fibroblast growth factor (FGF) and Notch signaling in influencing cell fate, assessing their impact on progenitor phenotype, cell-cycle kinetics, and layer specificity. Forced early cell-cycle exit, via Notch inhibition, caused rapid, near-exclusive generation of deep-layer VI neurons. In contrast, prolonged FGF2 promoted proliferation and maintained progenitor identity, delaying laminar progression via MAPK-dependent mechanisms. Inhibiting MAPK extended cell-cycle length and led to generation of layer-V CTIP2+ neurons by repressing alternative laminar fates. Taken together, FGF/MAPK regulates the proliferative/neurogenic balance in deep-layer corticogenesis and provides a resource for generating layer-specific neurons for studying development and disease.
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