Low concentrations of extracellular FGF-2 are sufficient but not essential for neurogenesis from human neural progenitor cells

• Published in: Molecular and cellular neuroscience Vol. 33; no. 1; pp. 29 - 35
• Main Authors: Nelson, Aaron D., Svendsen, Clive N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2006
• Subjects: Cell Differentiation - drug effects; Cell Division - physiology; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cyclic AMP Response Element-Binding Protein - metabolism; Dose-Response Relationship, Drug; Fibroblast Growth Factor 2 - pharmacology; Humans; Neurons - drug effects; Neurons - physiology; Stem Cells - drug effects; Stem Cells - physiology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2006.06.003

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.