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.
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 beta 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.
Ciccolini
F
F
Medical Research Council Cambridge Centre for Brain Repair, Cambridge CB2 2PY, England.
Svendsen
C N
CN
D000818:Animals; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007381:Intermediate Filament Proteins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation; D011247:Pregnancy; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects
D000911:Antibodies, Monoclonal; D017362:Cyclic AMP Response Element-Binding Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor