Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction.
Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction.
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发表时间：
1998-02
期刊：
影响因子：
4.6
通讯作者：
Xiaoling Xu;M. Weinstein;Cuiling Li;M. Naski;R. Cohen;D. Ornitz;P. Leder;C. Deng
中科院分区：
文献类型：
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作者：
Xiaoling Xu;M. Weinstein;Cuiling Li;M. Naski;R. Cohen;D. Ornitz;P. Leder;C. Deng
FGFR2是一种跨膜酪氨酸激酶，可作为成纤维细胞生长因子（FGF）家族成员的高亲和力受体。为了探索在发育中FGF/FGFR2信号的功能，我们通过删除了受体的整个免疫光蛋白样结构域III来突变FGFR2。我们表明，鼠FGFR2对于绒毛膜层毒素融合和胎盘滋养细胞增殖至关重要。 FGFR2（deltaigiii/deltaigiii）胚胎显示出两个不同的缺陷，导致形成功能性胎盘的故障。大约三分之一的突变体未能形成绒毛膜融合结，其余突变体没有胎盘的迷宫部分。因此，所有突变体在妊娠10-11天死亡。有趣的是，FGFR2（deltaigiii/deltaigiii）胚胎不会形成肢体芽。与此缺陷一致，在突变的假定肢体外胚层中不存在FGF8的表达（一种根尖外胚层因子），而在下层的中胚层中，调节了一种间质表达的肢体芽启动子FGF10的表达。这些发现提供了直接的遗传证据，表明脊椎动物肢体诱导绝对需要FGF/FGFR2信号，并且在肢体诱导过程中FGFR2信号对于FGF8和FGF10之间的相互调节环至关重要。
FGFR2 is a membrane-spanning tyrosine kinase that serves as a high affinity receptor for several members of the fibroblast growth factor (FGF) family. To explore functions of FGF/FGFR2 signals in development, we have mutated FGFR2 by deleting the entire immunoglobin-like domain III of the receptor. We showed that murine FGFR2 is essential for chorioallantoic fusion and placenta trophoblast cell proliferation. Fgfr2(DeltaIgIII/DeltaIgIII) embryos displayed two distinct defects that resulted in failures in formation of a functional placenta. About one third of the mutants failed to form the chorioallantoic fusion junction and the remaining mutants did not have the labyrinthine portion of the placenta. Consequently, all mutants died at 10-11 days of gestation. Interestingly, Fgfr2(DeltaIgIII/DeltaIgIII) embryos do not form limb buds. Consistent with this defect, the expression of Fgf8, an apical ectodermal factor, is absent in the mutant presumptive limb ectoderm, and the expression of Fgf10, a mesenchymally expressed limb bud initiator, is down regulated in the underlying mesoderm. These findings provide direct genetic evidence that FGF/FGFR2 signals are absolutely required for vertebrate limb induction and that an FGFR2 signal is essential for the reciprocal regulation loop between FGF8 and FGF10 during limb induction.