Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1.
Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1.
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音猬因子（Sonic Hedgehog）在不依赖Gli1的情况下诱导小鼠发生髓母细胞瘤。
DOI：
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发表时间：
2002-11
期刊：
影响因子：
11.2
通讯作者：
H. Weiner;R. Bakst;M. Hurlbert;Jason Ruggiero;Esther Ahn;W. S. Lee;Daniel N. Stephen;D. Zagzag;A. Joyner;D. Turnbull
中科院分区：
文献类型：
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作者：
H. Weiner;R. Bakst;M. Hurlbert;Jason Ruggiero;Esther Ahn;W. S. Lee;Daniel N. Stephen;D. Zagzag;A. Joyner;D. Turnbull
Sonic hedgehog （Shh）信号通路在小脑正常发育中起关键作用，并与髓母细胞瘤（常见的儿童小脑恶性肿瘤）有关。为了测试Shh错误表达是否足以导致成神经管细胞瘤的形成，我们使用超声生物显微镜引导下在子宫内将表达Shh的逆转录病毒注射到13.5天小鼠胚胎的小脑中，以证明直接激活Shh通路可导致肿瘤的形成。值得注意的是，76%的小鼠感染表达sh的逆转录病毒后出现成神经管细胞瘤。此外，与最近提出的Shh转录靶点Gli1在Shh诱导的肿瘤发生中起关键作用的观点相反，我们发现在Gli1零突变小鼠中形成成神经管细胞瘤。我们已经开发了一种高效的成神经管细胞瘤小鼠模型，并表明当Shh信号在该途径的上游被激活时，Gli1不需要肿瘤发生。
The Sonic hedgehog (Shh) signaling pathway plays a critical role in normal cerebellar development and has been implicated in medulloblastomas, common malignant childhood tumors of the cerebellum. To test whether Shh mis-expression is sufficient for medulloblastoma formation, we used ultrasound biomicroscopy-guided in utero injection of a Shh-expressing retrovirus into the cerebellum of 13.5-day mouse embryos to show that direct activation of the Shh pathway can lead to tumor formation. Significantly, medulloblastomas were observed in 76% of the mice infected with Shh-expressing retrovirus. Furthermore, contrary to recent suggestions that the Shh transcriptional target Gli1 plays a critical role in Shh-induced tumorigenesis, we found that medulloblastomas form in Gli1 null mutant mice. We have developed an efficient mouse model of medulloblastoma and shown that Gli1 is not required for tumorigenesis when Shh signaling is activated upstream in the pathway.