Adriamycin disruption of the Shh-Gli pathway is associated with abnormalities of foregut development
Adriamycin disruption of the Shh-Gli pathway is associated with abnormalities of foregut development
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DOI：
10.1016/j.jpedsurg.2004.08.013
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发表时间：
2004-12-01
影响因子：
2.4
通讯作者：
Beasley, S
中科院分区：
文献类型：
--
作者：
Arsic, D;Cameron, V;Beasley, S
背景：hedgehog信号通路在脊椎动物前肠的胚胎发生中起着至关重要的作用。Sonic hedgehog（Shh）蛋白和基因参与许多器官系统的分化，如脊索、底板和四肢;脊椎动物左右轴的发育;以及原始前肠的气管和食管的分化。方法：采用妊娠第6 ~ 9天的Sprague-Dawley胎鼠产前暴露阿霉素诱导食管闭锁和气管食管瘘。在妊娠第11至15天通过剖宫产收获胚胎。通过显微镜、解剖和连续组织学检查胚胎。结果：原位杂交结果显示阿霉素对Shh基因在大鼠胚胎中的表达有影响。阿霉素治疗的大鼠有畸形的脊索和未分割的前肠，和一些胚胎缺乏的背腹侧图案的Shh表达在control embryos.Conclusions：这些结果是一致的假设，阿霉素影响的Shh信号通路，导致中断的正常发育的前肠。(C)2004年爱思唯尔公司All rights reserved.
Background: The hedgehog signalling pathway appears to have a crucial role in the embryogenesis of the foregut in vertebrates. Sonic hedgehog (Shh) protein and gene are involved in the differentiation of many organ systems such as notochord, floor plate, and limbs; development of the left-right axis in vertebrates; and differentiation of trachea and esophagus from the primitive foregut.Methods: The prenatal exposure of Sprague-Dawley fetal rats to Adriamycin between days 6 and 9 of gestation was used to induce esophageal atresia and tracheoesophageal fistula. Embryos were harvested by cesarean section on gestational days 11 to 15. Embryos were examined by microscopy, dissection, and serial histology. In situ hybridization was used to study Shh gene expression in the rat embryos.Results: In situ hybridization showed that the pattern and level of Shh gene expression are affected by Adriamycin. Adriamycin-treated rats have deformed notochord and undivided foregut, and some of the embryos had a lack of the dorso-ventral patterning of Shh expression seen in control embryos.Conclusions: These results are consistent with the hypothesis that Adriamycin influences the Shh signalling pathway, resulting in disruption of normal development of the foregut. (C) 2004 Elsevier Inc. All rights reserved.