An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma
An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma
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DOI：
10.1593/neo.07891
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发表时间：
2008-01-01
期刊：
影响因子：
4.8
通讯作者：
Gulino, Alberto
中科院分区：
文献类型：
--
作者：
De Smaele, Enrico;Fragomeli, Caterina;Gulino, Alberto
髓母细胞瘤（MB）是最常见的恶性脑肿瘤的儿童所产生的失调小脑发育。Sonic Hedgehog（Shh）信号通路在小脑发育中起着重要作用，其异常表达已在MB中被证实。1- 14日龄小鼠小脑的基因表达谱揭示了一组基因，其表达与Hedgehog（HH）活性水平相关。从这个集群中，我们确定了Insm 1和Nhlh 1/NSCL 1作为新的HH目标诱导的Shh治疗培养的小脑颗粒祖细胞。发现Nhlh 1启动子被Gli 1转录因子结合并激活。值得注意的是，这些基因的表达在小鼠和人类HH依赖性MB中也上调，这表明它们可能是HH诱导的肿瘤发生过程的一部分或HH依赖性肿瘤细胞的特定性状。
Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh) pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH) activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.