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The Journal of Neuroscience, October 1, 1998, 18(19):7869-7880
Fibroblast Growth Factor 2 (FGF-2) Promotes Acquisition of
Epidermal Growth Factor (EGF) Responsiveness in Mouse Striatal
Precursor Cells: Identification of Neural Precursors Responding to both
EGF and FGF-2
Francesca
Ciccolini1, 2 and
Clive N.
Svendsen1
1 Medical Research Council Cambridge Centre for Brain
Repair, Cambridge CB2 2PY, England, and 2 Medical Research
Council Laboratory of Molecular Biology, Cambridge CB2 2QH, England
Epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2) induce the proliferation of neural precursor cells isolated from specific regions of the embryonic and adult brain. However, the
lineage relationship between the EGF- and FGF-2-responsive cells is
unknown. In this study we used phosphorylation of the transcription
factor cAMP response element-binding protein as a functional readout to
identify cells responding to EGF and FGF-2. In primary cultures of
mouse embryonic day 14 (E14) striatum, maintained in
vitro for 24 hr, 12% of the cells responded to FGF-2, whereas
no response to EGF could be detected. Seventy-five percent of these
FGF-2-responsive cells were  tubulin III (TuJ1)-positive neurons,
and 25% expressed nestin, a marker for neuroepithelial precursors.
After growth factor treatment for 6 d, a population of
nestin-positive cells responding to both EGF and FGF-2 were identified.
The 6-d-old cultures also contained a small number of TuJ1-positive
cells that responded to FGF-2 only. Priming of striatal cells for 24 hr
with FGF-2 but not with EGF was sufficient to induce the appearance of
EGF- and FGF-2 responsive cells after only 2 d in
vitro. Thus, neural precursor cells from the mouse E14 striatum
initially responding to FGF-2 only acquire EGF responsiveness later
during in vitro development. At this stage EGF and FGF-2 act on the same cells. The acquisition of EGF responsiveness is promoted by FGF-2.
Key words:
stem cells; progenitors; growth factors; CREB
phosphorylation; embryonic brain; neural development
Copyright © 1998 Society for Neuroscience 0270-6474/98/18197869-12$05.00/0
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