Expression patterns of Wnts, Frizzleds, sFRPs, and misexpression in transgenic mice suggesting a role for Wnts in pancreas and foregut pattern formation

Expression patterns of Wnts, Frizzleds, sFRPs, and misexpression in transgenic mice suggesting a role for Wnts in pancreas and foregut pattern formation
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DOI:
10.1002/dvdy.10157
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发表时间:
2002-11-01
影响因子:
2.5
通讯作者:
Serup, P
Serup, P
中科院分区:
生物学3区
文献类型:
--
作者:
Heller, RS;Dichmann, DS;Serup, P

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肠和胰腺的发育依赖于上皮间质的相互作用,这是公认的。我们在这里表明,几个Wnt,卷曲,和分泌卷曲相关蛋白(sFRP)编码的mRNA存在于小鼠胰腺形态发生。Wnt 5a和7 b mRNA在小鼠胚胎第10天左右开始在前肠间充质中广泛表达。其他表达的成员是Wnt 2b、Wnt 5 b和Wnt 11。此外,表达Wnt受体Frizzled 2、3、4、5、6、7、8和9的基因。为了了解Wnt在体内胰腺和前肠发育中的潜在功能,我们分析了在PDX-1基因启动子控制下表达Wnt 1和5a cDNA的转基因FO小鼠胎儿。在PDX-Wntl胎儿中,通常包括近端十二指肠的前肠区域反而类似于胃的后部延伸,通常与完全的胰腺和脾脏发育不全相关。此外,胃和十二指肠标志物的表达域之间的边界向后移动。在PDX-Wnt 5a胎仔中,源自近端前肠的几个结构尺寸减小,包括胰腺、脾脏和胃,而胃向十二指肠的过渡没有任何明显的移位。在这些胎仔中,整体胰腺形态发生变化,胰腺上皮致密致密,与Wnt 5A对细胞运动和/或附着的影响一致。两者合计,这些结果表明,Wnt基因参与上皮间充质信号传导,并可能指定区域的身份在前前肠。(C)2002 Wiley-Liss,Inc.
It is well established that gut and pancreas development depend on epithelialmesenchymal interactions. We show here that several Wnt, Frizzled, and secreted frizzled-related protein (sFRP) encoding mRNAs are present during mouse pancreatic morphogenesis. Wnt5a and 7b mRNA is broadly expressed in foregut mesenchyme starting around embryonic day 10 in mice. Other members expressed are Wnt2b, Wnt5b, and Wnt11. In addition, genes for the Wnt receptors, Frizzled2, 3, 4, 5, 6, 7, 8, and 9 are expressed. To understand potential Wnt functions in pancreas and foregut development in vivo, we analyzed transgenic FO mouse fetuses expressing Wnt1 and 5a cDNAs under control of the PDX-1 gene promoter. In PDX-Wntl fetuses, the foregut region normally comprising the proximal duodenum instead resembles a posterior extension of the stomach, often associated with complete pancreatic and splenic agenesis. Furthermore, the boundary between expression domains of gastric and duodenal markers is shifted in a posterior direction. In PDX-Wnt5a fetuses, several structures derived from the proximal foregut are reduced in size, including the pancreas, spleen, and stomach, without any apparent shift in the stomach to duodenum transition. In these fetuses, overall pancreatic Morphology is changed and the pancreatic epithelium is dense and compact, consistent with Wnt5A effects on cell movements and/or attachment. Taken together, these results suggest that Wnt genes participate in epithelial-mesenchymal signaling and may specify region identity in the anterior foregut. (C) 2002 Wiley-Liss, Inc.