Pancreas development is promoted by cyclopamine, a Hedgehog signaling inhibitor
Pancreas development is promoted by cyclopamine, a Hedgehog signaling inhibitor
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DOI：
10.1073/pnas.95.22.13036
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发表时间：
1998-10-27
影响因子：
11.1
通讯作者：
Melton, DA
中科院分区：
文献类型：
--
作者：
Kim, SK;Melton, DA
暴露于环巴胺，一种阻止Sonic hedgehog（Shh）信号传导的类固醇生物碱，促进胚胎小鸡的胰腺扩张。胰腺内分泌和外分泌结构的异位发育发生在邻近胰腺的区域，包括胃和十二指肠，并且胰腺中产生胰岛素的胰岛增大。胰腺发育所需的同源域转录因子PDX1在后前肠中广泛表达，但胰腺发育通常仅在表达PDX1的后前肠的限制区域中启动，其中内胚层Shh表达受到抑制。结果表明，环巴胺扩大了Shh信号传导不发生的内胚层区域，导致在PDX1表达的前肠内胚层的较大区域中的胰腺分化。环巴胺揭示了后胚胎前肠的广泛区域形成胰腺细胞的能力，并提供了扩大胚胎胰腺发育的手段。
Exposure to cyclopamine, a steroid alkaloid that blocks Sonic hedgehog (Shh) signaling, promotes pancreatic expansion in embryonic chicks. Heterotopic development of pancreatic endocrine and exocrine structures occurs in regions adjacent to the pancreas including stomach and duodenum, and insulin-producing islets in the pancreas are enlarged. The homeodomain transcription factor PDX1, required for pancreas development, is expressed broadly in the posterior foregut but pancreas development normally initiates only in a restricted region of PDX1-expressing posterior foregut where endodermal Shh expression is repressed. The results suggests that cyclopamine expands the endodermal region where Shh signaling does not occur, resulting in pancreatic differentiation in a larger region of PDX1-expressing foregut endoderm, Cyclopamine reveals the capacity of a broad region of the posterior embryonic foregut to form pancreatic cells and provides a means for expanding embryonic pancreas development.