Fgf9 signalling stimulates Spred and Sprouty expression in embryonic mouse pancreas mesenchyme
Fgf9 signalling stimulates Spred and Sprouty expression in embryonic mouse pancreas mesenchyme
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DOI：
10.1016/j.gep.2010.10.001
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发表时间：
2011-01-01
影响因子：
1.2
通讯作者：
Rescan, Claude
中科院分区：
文献类型：
--
作者：
Sylvestersen, Kathrine B.;Herrera, Pedro L.;Rescan, Claude
上皮-间充质相互作用对正常胰腺发育至关重要。成纤维细胞生长因子(Fgf)-10在胰腺间质中表达，其信号传导是胰腺上皮正常生长和基因表达调控所必需的。然而，人们对Fgf向间质传递信号知之甚少。在这里，我们研究了胚胎胰腺中不同剪接的Fgf受体异构体及其靶基因的表达：由Fgf信号诱导的Sprouty （Spry）和Spred家族基因。利用qPCR定量分析胰腺微解剖上皮和间质以及FACS分离的Pdx1-GFP（+）和- gfp（-）细胞群的mRNA水平，我们发现Spred和Sprouty家族的几个成员在胚胎小鼠胰腺中表达，并发现Spred1和-2以及Spry2和-4主要在胰腺间质中表达。通过胚胎胰腺外植体培养，我们发现Spred1/2和Spry2/4的表达受Fgf受体信号传导调节，并在Fgf9处理下增加，而在Fgf7或Fgf10处理下则不增加。我们扩展了先前的工作，表明Fgf9在胰腺间质中表达，并且由于已知Fgf9激活间质特异性的“c”-剪接形式的Fgf受体，而Fgf7和-10都激活上皮特异性的“b”-剪接形式的Fgf受体，这些结果表明Fgf信号传导在胰腺间质中是活跃的，其中Spred1/2和Spry2/4的表达出现在Fgf9信号传导的下游。(c) 2010 Elsevier B.V.保留所有权利。
Epithelial-mesenchymal interactions are critical for normal pancreas development. Fibroblast growth factor (Fgf)-10 is expressed in the pancreatic mesenchyme and its signalling is required for normal growth and regulation of gene expression in the pancreatic epithelium. However, little is known about putative Fgf signalling to the mesenchyme. Here we have examined the embryonic pancreas expression of differentially spliced Fgf receptor isoforms and their targets: the Sprouty (Spry) and Spred family genes which are induced by Fgf signalling. Using qPCR to quantify mRNA levels in microdissected pancreatic epithelium and mesenchyme as well as in FACS isolated Pdx1-GFP(+) and -GFP(-) cell populations we demonstrate that several members of the Spred and Sprouty families are expressed in embryonic mouse pancreas and find Spred1 and -2 as well as Spry2 and -4 to be predominantly expressed in pancreatic mesenchyme. Using embryonic pancreas explant cultures we demonstrate that Spred1/2 and Spry2/4 expression is regulated by Fgf receptor signalling and is increased by treatment with Fgf9, but not by Fgf7 or Fgf10. We extend previous work showing that Fgf9 is expressed in pancreatic mesenchyme, and since Fgf9 is known to activate the mesenchyme-specific "c"-splice forms of Fgf receptors, while Fgf7 and -10 both activate the epithelium-specific "b"-splice forms of Fgf receptors, these results suggest that Fgf signalling is active in the pancreatic mesenchyme, where expression of Spred1/2 and Spry2/4 appear downstream of Fgf9 signalling. (c) 2010 Elsevier B.V. All rights reserved.