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FGF-MAPK signaling regulates human deep-layer corticogenesis.

Carlos W Gantner1, Cameron P J Hunt1, Jonathan C Niclis1

  • 1The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3010, Australia.

Stem Cell Reports
|April 9, 2021
PubMed
Summary

Fibroblast growth factor (FGF) and Notch signaling control how cortical stem cells develop into specific neuron layers. FGF signaling promotes proliferation, while Notch inhibition drives deep-layer neuron generation.

Keywords:
MAPK signalingNotchcortexfibroblast growth factor 2human neural developmentlaminationneurogenesisstem cells

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Area of Science:

  • Developmental Neuroscience
  • Stem Cell Biology
  • Cortical Development

Background:

  • Mammalian cortical development involves generating diverse neurons from a common progenitor pool.
  • The mechanisms by which cortical progenitors change their potential to generate neurons of specific layers over time are not fully understood.

Purpose of the Study:

  • To investigate the roles of fibroblast growth factor (FGF) and Notch signaling in human embryonic stem cell-derived cortical progenitors.
  • To determine how these signaling pathways influence progenitor phenotype, cell-cycle kinetics, and neuronal layer specificity.

Main Methods:

  • Utilized human embryonic stem cell-derived cortical progenitors.
  • Manipulated FGF and Notch signaling pathways.
  • Assessed progenitor cell-cycle kinetics, phenotype, and resulting neuronal layer identity (e.g., layer VI, layer V CTIP2+ neurons).

Main Results:

  • Notch inhibition led to rapid cell-cycle exit and exclusive generation of deep-layer VI neurons.
  • Prolonged FGF2 signaling promoted progenitor proliferation and delayed laminar progression via MAPK-dependent pathways.
  • MAPK inhibition extended cell-cycle length, promoting layer V CTIP2+ neuron generation by suppressing alternative fates.

Conclusions:

  • FGF/MAPK signaling critically regulates the balance between proliferation and neurogenesis in deep-layer corticogenesis.
  • These findings offer insights into generating layer-specific neurons for studying cortical development and neurological diseases.