Generation of spinal motor neurons from human fetal brain‐derived neural stem cells: Role of basic fibroblast growth factor
- 19 September 2008
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 87 (2), 318-332
- https://doi.org/10.1002/jnr.21856
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.Keywords
This publication has 57 references indexed in Scilit:
- Astrocytes enhance long‐term survival of cholinergic neurons differentiated from human fetal neural stem cellsJournal of Neuroscience Research, 2007
- Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tubePhilosophical Transactions Of The Royal Society B-Biological Sciences, 2007
- Induction of oligodendrocyte progenitors in dorsal forebrain by intraventricular microinjection of FGF-2Developmental Biology, 2006
- The cellular fate of cortical progenitors is not maintained in neurosphere culturesMolecular and Cellular Neuroscience, 2005
- Stage-specific changes in gene expression in acutely isolated mouse CNS progenitor cellsDevelopmental Biology, 2005
- Intrinsic differences distinguish transiently neurogenic progenitors from neural stem cells in the early postnatal brainDevelopmental Biology, 2004
- Fibroblast growth factors and their receptors in the central nervous systemCell and tissue research, 2003
- Directed Differentiation of Embryonic Stem Cells into Motor NeuronsCell, 2002
- Neural induction, the default model and embryonic stem cellsNature Reviews Neuroscience, 2002
- Neuronal specification in the spinal cord: inductive signals and transcriptional codesNature Reviews Genetics, 2000