Fgf2在人类和小鼠胚胎脉络丛中表达，并影响脉络丛上皮细胞的行为。
Fgf2 is expressed in human and murine embryonic choroid plexus and affects choroid plexus epithelial cell behaviour.
作者信息
Greenwood Sarah, Swetloff Adam, Wade Angela M, Terasaki Tetsuya, Ferretti Patrizia
机构信息
DevelopmentalBiology Unit UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
出版信息
Cerebrospinal Fluid Res. 2008 Dec 29;5:20. doi: 10.1186/1743-8454-5-20.
BACKGROUND
Although fibroblast growth factor (Fgf) signalling plays crucial roles in several developing and mature tissues, little information is currently available on expression of Fgf2 during early choroid plexus development and whether Fgf2 directly affects the behaviour of the choroid plexus epithelium (CPe). The purpose of this study was to investigate expression of Fgf2 in rodent and human developing CPe and possible function of Fgf2, using in vitro models. The application of Fgf2 to brain in vivo can affect the whole tissue, making it difficult to assess specific responses of the CPe.
METHODS
Expression of Fgf2 was studied by immunohistochemistry in rodent and human embryonic choroid plexus. Effects of Fgf2 on growth, secretion, aggregation and gene expression was investigated using rodent CPe vesicles, a three-dimensional polarized culture model that closely mimics CPe properties in vivo, and rodent CPe monolayer cultures.
RESULTS
Fgf2 was present early in development of the choroid plexus both in mouse and human, suggesting the importance of this ligand in Fgf signalling in the developing choroid plexus. Parallel analysis of Fgf2 expression and cell proliferation during CP development suggests that Fgf2 is not involved in CPe proliferation in vivo. Consistent with this observation is the failure of Fgf2 to increase proliferation in the tri-dimensional vesicle culture model. The CPe however, can respond to Fgf2 treatment, as the diameter of CPe vesicles is significantly increased by treatment with this growth factor. We show that this is due to an increase in cell aggregation during vesicle formation rather than increased secretion into the vesicle lumen. Finally, Fgf2 regulates expression of the CPe-associated transcription factors, Foxj1 and E2f5, whereas transthyretin, a marker of secretory activity, is not affected by Fgf2 treatment.
CONCLUSION
Fgf2 expression early in the development of both human and rodent choroid plexus, and its ability to modulate behaviour and gene expression in CPe, supports the view that Fgf signalling plays a role in the maintenance of integrity and function of this specialized epithelium, and that this role is conserved between rodents and humans.
背景
尽管成纤维细胞生长因子（Fgf）信号通路在多个发育中和成熟组织中发挥关键作用，但目前关于Fgf2在脉络丛早期发育过程中的表达情况以及Fgf2是否直接影响脉络丛上皮（CPe）行为的信息很少。本研究的目的是使用体外模型研究Fgf2在啮齿动物和人类发育中的CPe中的表达以及Fgf2的可能功能。在体内将Fgf2应用于大脑会影响整个组织，因此难以评估CPe的特定反应。
方法
通过免疫组织化学研究Fgf2在啮齿动物和人类胚胎脉络丛中的表达。使用啮齿动物CPe囊泡（一种紧密模拟体内CPe特性的三维极化培养模型）和啮齿动物CPe单层培养物，研究Fgf2对生长、分泌、聚集和基因表达的影响。
结果
Fgf2在小鼠和人类脉络丛发育早期均有表达，表明该配体在发育中的脉络丛Fgf信号通路中具有重要性。在CP发育过程中对Fgf2表达和细胞增殖的平行分析表明，Fgf2不参与体内CPe的增殖。与此观察结果一致的是，Fgf2未能在三维囊泡培养模型中增加增殖。然而，CPe可以对Fgf2处理产生反应，因为用这种生长因子处理后CPe囊泡的直径显著增加。我们表明，这是由于囊泡形成过程中细胞聚集增加，而不是向囊泡腔内的分泌增加。最后，Fgf2调节CPe相关转录因子Foxj1和E2f5的表达，而分泌活性标志物转甲状腺素不受Fgf2处理的影响。
结论
Fgf2在人类和啮齿动物脉络丛发育早期的表达及其调节CPe行为和基因表达的能力支持以下观点：Fgf信号通路在维持这种特殊上皮的完整性和功能中起作用，并且这种作用在啮齿动物和人类之间是保守的。
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