title: Low concentrations of extracellular FGF-2 are sufficient but not essential for neurogenesis from human neural progenitor cells.
abstract: Secreted soluble growth factors have long been implicated in regulating or modulating cortical neurogenesis through stimulation of neurogenic progenitors. How a cortical progenitor cell interprets the growth factor signal may determine the progeny produced by the progenitor through a critical final round of cell division prior to terminal differentiation. Given that low concentrations of fibroblast growth factor 2 (FGF-2) have previously been shown to stimulate cortically derived rodent progenitors to produce neuroblasts, we hypothesized that low levels of FGF-2 may also promote neurogenesis from human neural progenitor cells (hNPC). hNPC were generated from the developing human cortex and maintained in epidermal growth factor as neurospheres. CREB phosphorylation revealed that a similar number of differentiating hNPC were stimulated by both low (2 pg/ml) and high (20 ng/ml) levels of FGF-2. The majority of progenitor cells that produced neurons underwent a final round of division during differentiation. Low concentrations of FGF-2 increased neurogenesis while high levels of FGF-2 maintained progenitor cell proliferation and blocked neurogenesis. Application of an FGF-2 neutralizing antibody during differentiation completely inhibited CREB phosphorylation but did not block neurogenesis. Thus, while low levels of FGF-2 can increase neurogenesis; extracellular stimulation by this factor is not required for new neuron production from hNPC.
authors.affiliation: Neuroscience Training Program, University of Wisconsin-Madison, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Nelson
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016222:Fibroblast Growth Factor 2