Effect of retinoic acid signaling on Wnt/beta-catenin and FGF signaling during body axis extension.

Effect of retinoic acid signaling on Wnt/beta-catenin and FGF signaling during body axis extension.
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DOI:
10.1016/j.gep.2009.06.003
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发表时间:
2009-09
期刊:
Gene expression patterns : GEP
影响因子:
--
通讯作者:
Duester G
Duester G
中科院分区:
其他
文献类型:
--
作者:
Zhao X;Duester G

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由维甲酸(RA)、Wnt/β-catenin和成纤维细胞生长因子(FGF)调控的细胞信号在体轴延伸过程中很重要,并且这些途径之间存在相互作用。在somite早期阶段,Wnt/β-catenin和FGF信号域存在于发育主干的前部和后部,而RA信号在RA合成酶retinaldehyde dehydrogenase-2 (Raldh2)的控制下发生在主干的两者之间。先前的研究表明,缺乏维生素A的鹌鹑胚胎和缺乏RA合成的Raldh2−/−小鼠胚胎在发育中的躯干中表现出Fgf8和Wnt8a的异位表达。在这里,我们证明Raldh2−/−小鼠胚胎通过Sprouty2和Pea3的表达显示FGF信号进入躯干的扩展,并且通过Axin2, Tbx6, Cdx2和Cdx4的表达检测Wnt/β-catenin信号的扩展。RA信号缺失后,Fgf8、Wnt8a和Wnt3a的尾侧表达域向前扩展至主干,但Fgf4或Fgf17的尾侧表达无变化,Fgf18和Cdx1的尾侧表达减少。这些发现提示RA在发育主干中抑制Fgf8、Wnt8a和Wnt3a可随着体轴的延伸下调FGF信号和Wnt/β-catenin信号。
Cell-cell signaling regulated by retinoic acid (RA), Wnt/β-catenin, and fibroblast growth factor (FGF) is important during body axis extension, and interactions between these pathways have been suggested. At early somite stages, Wnt/β-catenin and FGF signaling domains exist both anterior and posterior to the developing trunk, whereas RA signaling occurs in between in the trunk under the control of the RA-synthesizing enzyme retinaldehyde dehydrogenase-2 (Raldh2). Previous studies demonstrated that vitamin A deficient quail embryos and Raldh2−/− mouse embryos lacking RA synthesis exhibit ectopic expression of Fgf8 and Wnt8a in the developing trunk. Here, we demonstrate that Raldh2−/− mouse embryos display an expansion of FGF signaling into the trunk monitored by Sprouty2 and Pea3 expression, and an expansion of Wnt/β-catenin signaling detected by expression of Axin2, Tbx6, Cdx2, and Cdx4. Following loss of RA signaling, the caudal expression domains of Fgf8, Wnt8a, and Wnt3a expand anteriorly into the trunk, but no change is observed in caudal expression of Fgf4 or Fgf17 plus caudal expression of Fgf18 and Cdx1 is reduced. These findings suggest that RA repression of Fgf8, Wnt8a, and Wnt3a in the developing trunk functions to down-regulate FGF signaling and Wnt/β-catenin signaling as the body axis extends.
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