Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.
Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.
复制标题
异常脊索分层对阿霉素小鼠模型后肠发育的影响。
DOI：
10.1007/s00383-013-3386-5
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发表时间：
2013
影响因子：
1.8
通讯作者：
Hiroaki Kitagawa
中科院分区：
文献类型：
--
作者：
Hideaki Sato;Piotr Hajduk ;Shigeyuki Furuta;Munechika Wakisaka;Paula Murphy;Prem Puri;Hiroaki Kitagawa
背景阿霉素小鼠模型（AMM）是一种血管畸形模型。来源于脊索的Sonic hedgehog（Shh）通路与肛门直肠畸形有关。我们假设在AMM中观察到的后肠异常的结果异常的notochord.MethodsTime-mated CBA/Ca小鼠接受两次腹腔注射阿霉素（6 mg/kg）或生理盐水作为对照胚胎天（E）7和8。从E9至E11收获胎仔，在用标记的RNA探针进行整体原位杂交后染色以检测Shhand Fork头盒F1（Foxf 1）转录物。使用内胚层标记物Hnf 3 β的免疫定位来可视化形态。OPT扫描胚胎，获得3D representations of expressions.ResultsIn AMM，脊索异常位移腹侧与附件的后肠内胚层在71%的标本。在32%的处理胚胎中，异常后肠以囊状结构盲状结束，在29%的处理胚胎中，两种类型均可见。EndodermalShhand mesenchymalFoxf 1基因的表达被保存在后肠囊状畸形周围。ConclusionsThe delamination of the developing notochord in the AMM is disrupted，这可能会影响从脊索到后肠的信号传导机制，导致后肠的异常模式。
BackgroundAdriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal malformations. We hypothesized hindgut anomalies observed in the AMM are the result of abnormal effect of the notochord.MethodsTime-mated CBA/Ca mice received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11, stained following whole mount in situ hybridization with labeled RNA probes to detectShhand Fork head box F1(Foxf1) transcripts. Immunolocalization with endoderm marker Hnf3β was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of expressions.ResultsIn AMM, the notochord was abnormally displaced ventrally with attachment to the hindgut endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal hindgut ended blindly in a cystic structure, and both of types were remarked in 29 % of treated embryos. EndodermalShhand mesenchymalFoxf1genes expression were preserved around the hindgut cystic malformation.ConclusionsThe delamination of the developing notochord in the AMM is disrupted, which may influence signaling mechanisms from the notochord to the hindgut resulting in abnormal patterning of the hindgut.