Fibroblast growth factor 2 maintains the neurogenic capacity of embryonic neural progenitor cells in vitro but changes their neuronal subtype specification.
Many in vitro systems used to examine multipotential neural progenitor cells (NPCs) rely on mitogens including fibroblast growth factor 2 (FGF2) for their continued expansion. However, FGF2 has also been shown to alter the expression of transcription factors (TFs) that determine cell fate. Here, we report that NPCs from the embryonic telencephalon grown without FGF2 retain many of their in vivo characteristics, making them a good model for investigating molecular mechanisms involved in cell fate specification and differentiation. However, exposure of cortical NPCs to FGF2 results in a profound change in the types of neurons generated, switching them from a glutamatergic to a GABAergic phenotype. This change closely correlates with the dramatic upregulation of TFs more characteristic of ventral telencephalic NPCs. In addition, exposure of cortical NPCs to FGF2 maintains their neurogenic potential in vitro, and NPCs spontaneously undergo differentiation following FGF2 withdrawal. These results highlight the importance of TFs in determining the types of neurons generated by NPCs in vitro. In addition, they show that FGF2, as well as acting as a mitogen, changes the developmental capabilities of NPCs. These findings have implications for the cell fate specification of in vitro-expanded NPCs and their ability to generate specific cell types for therapeutic applications. Disclosure of potential conflicts of interest is found at the end of this article.
Bithell
Angela
A
Centre for the Cellular Basis of Behaviour, MRC Centre for Neurodegeneration Research, The James Black Centre, King's College London, Institute of Psychiatry, 125 Coldharbour Lane, London SE5 9NU, United Kingdom.
Finch
Sophie E
SE
Hornby
Matthew F
MF
Williams
Brenda P
BP
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000502:physiology; D004253:DNA Nucleotidylexotransferase; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D007381:Intermediate Filament Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
D015415:Biomarkers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D014157:Transcription Factors; D012313:RNA; D004253:DNA Nucleotidylexotransferase