The roles of FGF signaling in germ cell migration in the mouse
The roles of FGF signaling in germ cell migration in the mouse
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DOI：
10.1242/dev.02080
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发表时间：
2005-12-01
期刊：
影响因子：
4.6
通讯作者：
Wylie, C
中科院分区：
文献类型：
--
作者：
Takeuchi, Y;Molyneaux, K;Wylie, C
成纤维细胞生长因子（FGF）信号被认为在生殖细胞行为中起作用。据报道，FGF 2是体外原始生殖细胞的促分裂原，而FGF 2、钢因子和LIF的组合导致培养的生殖细胞转化成类似ES细胞的多能细胞的永久系。然而，FGF信号传导在体内迁移的生殖细胞上的实际功能是未知的。我们显示，通过RT-PCR分析纯化的E10.5生殖细胞的cDNA，生殖细胞表达两种FGF受体：Fgfr 1-IIIc和Fgfr 2-IIIb。其次，我们发现FGF介导的MAP激酶通路的激活发生在生殖细胞迁移过程中，因此它们是FGF信号传导的潜在直接靶点。第三，我们在简单的功能获得实验中使用培养的胚胎切片，使用FGF配体，以表明FGF 2，FGFR 1-IIIc的配体，影响运动性，而FGF 7，FGFR 2-IIIb的配体，影响生殖细胞数量。使用FGF信号传导的特异性抑制剂，功能丧失导致迁移的生殖细胞中细胞凋亡增加和细胞形状改变的抑制。最后，我们通过检查携带FGFR 2-IIIb功能丧失等位基因的胚胎中生殖细胞的位置和数量，在体内证实了体外切片培养中观察到的效果。在FGFR 2-IIIb（-/-）胚胎中，生殖细胞迁移不受影响，但生殖细胞数量显著减少。这些数据表明，通过FGFR 2-IIIb的FGF信号传导的主要作用是控制生殖细胞数量。这些数据没有区分FGF信号对生殖细胞的直接和间接影响，两者都可能参与其中。
Fibroblast growth factor (FGF) signaling is thought to play a role in germ cell behavior. FGF2 has been reported to be a mitogen for primordial germ cells in vitro, whilst combinations of FGF2, steel factor and LIF cause cultured germ cells to transform into permanent lines of pluripotent cells resembling ES cells. However, the actual function of FGF signaling on the migrating germ cells in vivo is unknown. We show, by RT-PCR analysis of cDNA from purified E10.5 germ cells, that germ cells express two FGF receptors: Fgfr1-IIIc and Fgfr2-IIIb. Second, we show that FGF-mediated activation of the MAP kinase pathway occurs in germ cells during their migration, and thus they are potentially direct targets of FGF signaling. Third, we use cultured embryo slices in simple gain-of-function experiments, using FGF ligands, to show that FGF2, a ligand for FGFR1-IIIc, affects motility, whereas FGF7, a ligand for FGFR2-IIIb, affects germ cell numbers. Loss of function, using a specific inhibitor of FGF signaling, causes increased apoptosis and inhibition of cell shape change in the migrating germ cells. Lastly, we confirm in vivo the effects seen in slice cultures in vitro, by examining germ cell positions and numbers in embryos carrying a loss-of-function allele of FGFR2-IIIb. In FGFR2-IIIb(-/-) embryos, germ cell migration is unaffected, but the numbers of germ cells are significantly reduced. These data show that a major role of FGF signaling through FGFR2-IIIb is to control germ cell numbers. The data do not discriminate between direct and indirect effects of FGF signaling on germ cells, and both may be involved.