FGF-8 isoforms activate receptor splice forms that are expressed in mesenchymal regions of mouse development.
FGF-8 isoforms activate receptor splice forms that are expressed in mesenchymal regions of mouse development.
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发表时间：
1995-11
期刊：
影响因子：
4.6
通讯作者：
C. MacArthur;Avril A. Lawshé;Jingsong Xu;Sylvia Santos-Ocampo;M. Heikinheimo;A. Chellaiah;D. Ornitz
中科院分区：
文献类型：
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作者：
C. MacArthur;Avril A. Lawshé;Jingsong Xu;Sylvia Santos-Ocampo;M. Heikinheimo;A. Chellaiah;D. Ornitz
Fgf8 基因在发育中的四肢和颅面结构中表达，这些区域已知对小鼠胚胎的生长和模式很重要。尽管 Fgf8 被选择性剪接以产生至少 7 种仅在成熟氨基末端不同的分泌同工型，但这些多种同工型的生物学意义尚不清楚。在本报告中，我们证明在小鼠发育过程中 Fgf8 表达位点存在多种 FGF-8 亚型。为了解决 FGF-8 亚型可能与不同成纤维细胞生长因子受体相互作用的可能性，我们制备了重组 FGF-8 蛋白亚型。我们检查了这些蛋白质激活选择性剪接形式的成纤维细胞生长因子受体 1-3 和成纤维细胞生长因子受体 4 的能力。重组 FGF-8b 和 FGF-8c 激活 FGFR3 和 FGFR4 的“c”剪接形式，而 FGF-8b 还有效激活 FGFR2 的“c”剪接形式。没有检测到重组或细胞表达的 FGF-8a 的活性。此外，所测试的同工型均未与 FGFR1-3 的“b”剪接形式或 FGFR1 的“c”剪接形式有效相互作用。这些结果表明，由外胚层衍生的上皮细胞产生的 FGF-8b 和 FGF-8c 亚型与间充质表达的成纤维细胞生长因子受体相互作用。因此，FGF-8b 和 FGF-8c 可能在肢体和颅面发育过程中向底层间充质提供有丝分裂信号。
The Fgf8 gene is expressed in developing limb and craniofacial structures, regions known to be important for growth and patterning of the mouse embryo. Although Fgf8 is alternatively spliced to generate at least 7 secreted isoforms that differ only at their mature amino terminus, the biological significance of these multiple isoforms is not known. In this report, we demonstrate that multiple FGF-8 isoforms are present at sites of Fgf8 expression during mouse development. To address the possibility that the FGF-8 isoforms might interact with different fibroblast growth factor receptors, we prepared recombinant FGF-8 protein isoforms. We examined the ability of these proteins to activate alternatively spliced forms of fibroblast growth factor receptors 1-3, and fibroblast growth factor receptor 4. Recombinant FGF-8b and FGF-8c activate the 'c' splice form of FGFR3, and FGFR4, while FGF-8b also efficiently activates 'c' splice form of FGFR2. No activity could be detected for recombinant or cell expressed FGF-8a. Furthermore, none of the isoforms tested interact efficiently with 'b' splice forms of FGFR1-3, or the 'c' splice form of FGFR1. These results indicate that the FGF-8b and FGF-8c isoforms, produced by ectodermally derived epithelial cells, interact with mesenchymally expressed fibroblast growth factor receptors. FGF-8b and FGF-8c may therefore provide a mitogenic signal to the underlying mesenchyme during limb and craniofacial development.