FGF-MAPK signaling regulates human deep-layer corticogenesis

• DOI: 10.1016/j.stemcr.2021.03.014
• Publication Date: 2021-04-08T14:34:56Z
• Authors: Carlos W. Gantner; Cameron P.J. Hunt; Jonathan C. Niclis; Vanessa Penna; Stuart J. McDougall; Lachlan H. Thompson; Clare L. Parish
• Keywords: Corticogenesis

Despite heterogeneity across the six layers of mammalian cortex, all excitatory neurons are generated from a single founder population neuroepithelial stem cells. However, how these progenitors alter their layer competence over time remains unknown. Here, we used human embryonic cell-derived cortical to examine role fibroblast growth factor (FGF) and Notch signaling in influencing cell fate, assessing impact on progenitor phenotype, cell-cycle kinetics, specificity. Forced early exit, via inhibition, caused rapid, near-exclusive generation deep-layer VI neurons. In contrast, prolonged FGF2 promoted proliferation maintained identity, delaying laminar progression MAPK-dependent mechanisms. Inhibiting MAPK extended length led layer-V CTIP2+ by repressing alternative fates. Taken together, FGF/MAPK regulates proliferative/neurogenic balance corticogenesis provides resource for generating layer-specific studying development disease.