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Analysis on the gene expression and the function of FGFs and FGF receptors during induction of differentiation of embryonal carcinoma cells.

FGF及FGF受体在胚胎癌细胞诱导分化过程中的基因表达及功能分析

基本信息

批准号：
06680701
负责人：
SEO Misuzu
金额：
$ 0.26万
依托单位：
Kyoto Sangyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The changes in the gene expression of fibroblast growth factors (FGFs) and the receptors for FGFs (FGFRs) during retinoic acid-induced neuronal differentiation of mouse embryonal carcinoma -derived P19 cells (EC P19) were examined in this study. EC P19 cells are pluripotent and can be induced to differentiate into neurons and glia cells by exposing cell aggregates to retinoic acid (RA) at 10^<-7> M to 10^<-6>M concentraitons. These neurons resemble morphologically those in the central nervous system, and many neuron-specific genes were shown to be expressed in those cells. Thus, the above system is a good model for studying in vitro what events occur during the critical phase of neuronal differentiation. Gene expression of three FGFs, including FGF2, FGF6, and FGF9 was increased on induction of neuronal differentiation of P19 cells. Among FGFRs, the gene expression of FGFR2 was greatly increased, while that of FGFR1 was constant. Formation of cell aggregates without RA treatment was no … More t enough to induce neuronal differentiation ; most of the cells remained undifferentiated, but a small portion of the cells became heart muscle cells. Under these conditions these FGFs were not induced. In contrast, FGF5 and FGF8 were greatly increased in their expression. Thus, FGF2, FGF6, and FGF9 may play important roles in neuronal development, for example, stimulating growth, survival, and cell-cell adhesion. Among these FGFs, the sequence of mouse FGF9 cDNA expressed in the cells induced by RA was first reported. The murine cDNA showed 92.4% nucleotide sequence homology to the human FGF9 cDNA and 98.2% homology to that of rats. This mouse FGF9 cDNA encoded a polypeptide consisting of 208 amino acids with amino acid sequence identical to that of rats. Only one amino acid was replaced compared to the human homolog. The highly conserved sequence homology of FGF9 suggests its functional importance.The protein expression of FGF9 during the neuronal differentiation of P19 cells was also examined by staining the cells with anti-FGF9 antibody. Neurons were strongly stained with the antibody, and glial cells were also stained. This study suggests that FGF9 plays important roles in neuronal development, for example, stimulating growth and maintenance of the function of neurons and glial cells. Less

本研究观察了维甲酸诱导小鼠胚胎癌源性P19细胞(EC P19)分化过程中成纤维细胞生长因子(FGFs)及其受体(FGFRs)基因表达的变化。EC P19细胞具有多能性，可通过维甲酸(RA)暴露于10^lt；-6&gt；M浓度的维甲酸诱导其分化为神经元和胶质细胞。这些神经元在形态上与中枢神经系统中的神经元相似，许多神经元特异性基因在这些细胞中表达。因此，上述系统是一个很好的模型，在体外研究在神经元分化的关键阶段发生了什么事件。诱导P19细胞向神经元分化时，FGF2、FGF6和FGF9的基因表达增加。在FGFRs中，FGFR2的基因表达显著增加，而FGFR1的基因表达不变。未经RA处理的细胞聚集体的形成不是…更多的T细胞足以诱导神经元分化；大多数细胞仍未分化，但一小部分细胞成为心肌细胞。在这些条件下，这些FGFs没有被诱导。相反，FGF5和FGF8的表达显著增加。因此，FGF2、FGF6和FGF9可能在神经元发育中发挥重要作用，例如刺激生长、存活和细胞-细胞黏附。其中，小鼠成纤维细胞生长因子9在维甲酸诱导的细胞中表达的序列为首次报道。小鼠与人FGF9的核苷酸序列同源性为92.4%，与大鼠的同源性为98.2%。小鼠FGF9基因编码208个氨基酸组成的多肽，氨基酸序列与大鼠一致。与人类同源物相比，只有一种氨基酸被替换。FGF9高度保守的序列同源性表明了其功能的重要性。用抗FGF9抗体染色检测了P19细胞神经分化过程中FGF9的蛋白表达。抗体对神经元呈强阳性反应，对胶质细胞也呈阳性反应。本研究提示，FGF9在神经元发育中起重要作用，如刺激神经元生长和维持神经元和神经胶质细胞的功能。较少