Generation of spinal motor neurons from human fetal brain-derived neural stem cells: Role of basic fibroblast growth factor

Paivi M. Jordan, Luis D. Ojeda, Jason R. Thonhoff, Junling Gao, Darren Boehning, Yongjia Yu, Ping Wu

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Neural stem cells (NSCs) have some specified properties but are generally uncommitted and so can change their fate after exposure to environmental cues. It is unclear to what extent this NSC plasticity can be modulated by extrinsic cues and what are the molecular mechanisms underlying neuronal fate determination. Basic fibroblast growth factor (bFGF) is a well-known mitogen for proliferating NSCs. However, its role in guiding stem cells for neuronal subtype specification is undefined. Here we report that in-vitro-expanded human fetal forebrain-derived NSCs can generate cholinergic neurons with spinal motor neuron properties when treated with bFGF within a specific time window. bFGF induces NSCs to express the motor neuron marker Hb9, which is blocked by specific FGF receptor inhibitors and bFGF neutralizing antibodies. This development of spinal motor neuron properties is independent of selective proliferation or survival and does not require high levels of MAPK activation. Thus our study indicates that bFGF can play an important role in modulating plasticity and neuronal fate of human NSCs and presumably has implications for exploring the full potential of brain NSCs for clinical applications, particularly in spinal motor neuron regeneration.

Original languageEnglish (US)
Pages (from-to)318-332
Number of pages15
JournalJournal of Neuroscience Research
Volume87
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • Basic fibroblast growth factor
  • Differentiation
  • Motor neuron
  • Neural stem cell
  • Plasticity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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