Lum Maggie, Turbic Alisa, Mitrovic Branka, Turnley Ann M
Centre for Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
J Neurosci Res. 2009 Aug 1;87(10):2201-10. doi: 10.1002/jnr.22047.
Fibroblast growth factor-9 (FGF9) is expressed in the CNS and is reported to be a mitogen for glial cells, to promote neuronal survival, and to retard oligodendrocyte differentiation. Here we examined the effects of FGF9 on the differentiation, survival, and proliferation of adult neural progenitor cells derived from the adult mouse subventricular zone. FGF9 by itself induced neurosphere proliferation, but its effects were modest compared with those of epidermal growth factor and FGF2. When neurospheres were dissociated and plated for differentiation, FGF9 increased total cell number over time in a dose-dependent manner. Ki67 immunostaining and bromodeoxyuridine incorporation indicated that this was at least partially due to the continued presence of proliferative nestin-positive neural progenitor cells and betaIII tubulin-positive neuronal precursors. FGF9 also promoted cell survival as indicated by a decreased number of TUNEL-positive cells over time. Assessment of differentiation showed that FGF9 increased neuron generation that reflected the increase in total cell number; however, the percentage of progenitor cells differentiating into neurons was slightly decreased. FGF9 had a modest effect on oligodendrocyte generation, although it appeared to slow the maturation of oligodenrocytes at higher concentrations. The most marked effect on differentiation was an almost total lack of glial fibrillary acidic protein (GFAP)-positive astrocytes up to 7 days following FGF9 addition, indicating that astrocyte differentiation was strongly inhibited. Total inhibition required prolonged treatment, although a 1-hr pulse was sufficient for partial inhibition, and bone morphogenic protein-4 could partially overcome the FGF9 inhibition of astrocyte differentiation. FGF9 therefore has multiple effects on adult neural precursor cell function, enhancing neuronal precursor proliferation and specifically inhibiting GFAP expression.
成纤维细胞生长因子9（FGF9）在中枢神经系统中表达，据报道它是一种神经胶质细胞有丝分裂原，可促进神经元存活，并延缓少突胶质细胞分化。在此，我们研究了FGF9对源自成年小鼠脑室下区的成年神经祖细胞的分化、存活和增殖的影响。FGF9自身可诱导神经球增殖，但其作用与表皮生长因子和FGF2相比相对较弱。当神经球解离并铺板进行分化时，FGF9可使总细胞数随时间呈剂量依赖性增加。Ki67免疫染色和溴脱氧尿苷掺入表明，这至少部分是由于增殖性巢蛋白阳性神经祖细胞和βIII微管蛋白阳性神经元前体细胞持续存在所致。FGF9还可促进细胞存活，随着时间推移，TUNEL阳性细胞数量减少即表明了这一点。分化评估显示，FGF9增加了神经元生成，这反映了总细胞数的增加；然而，祖细胞分化为神经元的百分比略有下降。FGF9对少突胶质细胞生成的影响较小，尽管在较高浓度下它似乎会减缓少突胶质细胞的成熟。对分化最显著的影响是，在添加FGF9后的7天内，几乎完全缺乏胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞，这表明星形胶质细胞分化受到强烈抑制。完全抑制需要长时间处理，尽管1小时的脉冲足以产生部分抑制作用，并且骨形态发生蛋白4可以部分克服FGF9对星形胶质细胞分化的抑制作用。因此，FGF9对成年神经前体细胞功能具有多种影响，可增强神经元前体细胞增殖并特异性抑制GFAP表达。
