Kim S K, Melton D A
Howard Hughes Medical Institute and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13036-41. doi: 10.1073/pnas.95.22.13036.
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.
环杷明是一种甾体生物碱，可阻断音猬因子（Shh）信号传导，胚胎期雏鸡接触环杷明可促进胰腺扩张。胰腺内分泌和外分泌结构会在包括胃和十二指肠在内的胰腺附近区域异位发育，且胰腺中产生胰岛素的胰岛会增大。胰腺发育所需的同源结构域转录因子PDX1在前肠后部广泛表达，但胰腺发育通常仅在PDX1表达的前肠后部的一个受限区域启动，该区域内胚层Shh表达受到抑制。结果表明，环杷明扩大了Shh信号不发生的内胚层区域，导致在表达PDX1的前肠内胚层更大区域发生胰腺分化。环杷明揭示了胚胎前肠后部广泛区域形成胰腺细胞的能力，并为扩大胚胎胰腺发育提供了一种方法。
