盲肠发育需要上皮-间充质FGF信号的相互作用。

Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development.

作者信息

Zhang Xiuqin, Stappenbeck Thaddeus S, White Andrew C, Lavine Kory J, Gordon Jeffrey I, Ornitz David M

机构信息

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.

出版信息

Development. 2006 Jan;133(1):173-80. doi: 10.1242/dev.02175. Epub 2005 Nov 24.

Abstract

Fibroblast growth factor (FGF) signaling mediates reciprocal mesenchymal-epithelial cell interactions in the developing mouse lung and limb. In the gastrointestinal (GI) tract, FGF10 is expressed in the cecal mesenchyme and signals to an epithelial splice form of FGF receptor (FGFR) 2 to regulate epithelial budding. Here, we identify FGF9 as a reciprocal epithelial-mesenchymal signal required for cecal morphogenesis. Fgf9 null (Fgf9(-/-)) mouse embryos have agenesis of the embryonic cecum, lacking both mesenchymal expansion and an epithelial bud. In the cecal region of Fgf9(-/-) embryos, mesenchymal expression of Fgf10 and Bmp4 is notably absent, whereas the expression of epithelial markers, such as sonic hedgehog, is not affected. Using epithelial and whole explant cultures, we show that FGF9 signals to mesenchymal FGFRs and that FGF10 signals to epithelial FGFRs. Taken together, these data show that an epithelial FGF9 signal is necessary for the expansion of cecal mesenchyme and the expression of mesenchymal genes that are required for epithelial budding. Thus, these data add to our understanding of FGF-mediated reciprocal epithelial-mesenchymal signaling.

摘要

成纤维细胞生长因子(FGF)信号传导介导发育中的小鼠肺和肢体中相互的间充质 - 上皮细胞相互作用。在胃肠道(GI)中,FGF10在盲肠间充质中表达,并向FGF受体(FGFR)2的上皮剪接形式发出信号,以调节上皮出芽。在这里,我们确定FGF9是盲肠形态发生所需的相互上皮 - 间充质信号。Fgf9基因敲除(Fgf9(-/-))小鼠胚胎出现胚胎盲肠发育不全,缺乏间充质扩张和上皮芽。在Fgf9(-/-)胚胎的盲肠区域,明显缺乏Fgf10和Bmp4的间充质表达,而诸如音猬因子等上皮标志物的表达不受影响。使用上皮和全组织外植体培养,我们表明FGF9向间充质FGFR发出信号,而FGF10向上皮FGFR发出信号。综上所述,这些数据表明上皮FGF9信号对于盲肠间充质的扩张以及上皮出芽所需的间充质基因的表达是必要的。因此,这些数据加深了我们对FGF介导的相互上皮 - 间充质信号传导的理解。

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