Bansal R, Kumar M, Murray K, Morrison R S, Pfeiffer S E
Department of Microbiology, University of Connecticut School of Medicine, Farmington 06030-3205, USA.
Mol Cell Neurosci. 1996 Apr;7(4):263-75. doi: 10.1006/mcne.1996.0020.
Fibroblast growth factors (FGFs) affect a broad spectrum of developmentally regulated cellular responses involved in the control of growth and differentiation. To identify specific FGF receptor forms involved in these responses, we have characterized FGF receptor transcript expression, and its modulation by FGF-2, as enriched populations of oligodendrocyte progenitors differentiate into mature oligodendrocytes. The data demonstrate that the levels of mRNA expression for FGF high-affinity receptors-1, -2, and -3 are differentially regulated during lineage progression: FGF receptor-1 expression increases with lineage progression, FGF receptor-2 is predominantly expressed by terminally differentiated oligodendrocytes, and FGF receptor-3 reaches a peak level of expression in late progenitors and then declines upon further differentiation; FGF receptor-4 expression was not detected in oligodendrocytes. Distinct patterns of alternatively spliced variants of FGF receptor-1 and -2 transcripts are expressed: the predominant FGF receptor-1 transcripts contain three Ig-like domains (FGF receptor-1 alpha), whereas the FGF receptor-2 transcripts contain two Ig-like domains (FGF receptor-2 beta 2) and this form is up-regulated as oligodendrocytes differentiate. In addition, the expression of these receptors is differentially regulated by the ligand, FGF-2: FGF receptor-1 mRNA expression is up-regulated in early progenitors, and FGF receptor-2 mRNA expression is down-regulated in mature oligodendrocytes. Finally, astrocytes express FGF receptor-1, -2, and -3 transcripts, but at different levels and with different exon utilization (FGF receptor-1 beta, FGF receptor-2 beta 1/beta 2) compared to oligodendrocytes. To our knowledge this is the first report that demonstrates that the mRNA expression of these three FGF receptor types is differentially regulated in primary cells as they differentiate along a lineage from progenitors to terminally differentiated cells. We propose that this pattern of expression provides a molecular basis for the developmentally varying response of cells to a common ligand. For example, according to this hypothesis, in response to FGF-2, FGF receptor-1 transduces signals that stimulate the prolonged proliferation and migration of early progenitors, FGF receptor-3 promotes the proliferation and arrest of differentiation of late progenitors, and FGF receptor-2 transduces signals for terminal differentiation, but not proliferation, in mature oligodendrocytes.
成纤维细胞生长因子（FGFs）影响广泛的发育调控细胞反应，这些反应参与生长和分化的控制。为了确定参与这些反应的特定FGF受体形式，我们对FGF受体转录本表达及其受FGF-2的调节进行了表征，此时少突胶质前体细胞富集群体正分化为成熟少突胶质细胞。数据表明，FGF高亲和力受体-1、-2和-3的mRNA表达水平在谱系进展过程中受到不同调节：FGF受体-1的表达随谱系进展而增加，FGF受体-2主要由终末分化的少突胶质细胞表达，FGF受体-3在晚期前体细胞中达到表达峰值，然后在进一步分化时下降；在少突胶质细胞中未检测到FGF受体-4的表达。FGF受体-1和-2转录本的可变剪接变体呈现出不同的表达模式：主要的FGF受体-1转录本包含三个免疫球蛋白样结构域（FGF受体-1α），而FGF受体-2转录本包含两个免疫球蛋白样结构域（FGF受体-2β2），并且这种形式在少突胶质细胞分化时上调。此外，这些受体的表达受到配体FGF-2的不同调节：FGF受体-1的mRNA表达在早期前体细胞中上调，而FGF受体-2的mRNA表达在成熟少突胶质细胞中下调。最后，星形胶质细胞表达FGF受体-1、-2和-3转录本，但与少突胶质细胞相比，其表达水平不同且外显子利用方式不同（FGF受体-1β、FGF受体-2β1/β2）。据我们所知，这是第一份表明这三种FGF受体类型的mRNA表达在原代细胞从祖细胞向终末分化细胞沿谱系分化过程中受到不同调节的报告。我们提出这种表达模式为细胞对共同配体的发育性不同反应提供了分子基础。例如，根据这一假设，响应FGF-2时，FGF受体-1转导刺激早期前体细胞长期增殖和迁移的信号，FGF受体-3促进晚期前体细胞的增殖并阻止其分化，而FGF受体-2在成熟少突胶质细胞中转导终末分化而非增殖的信号。
