Transcriptional responses of zebrafish embryos exposed to potential sonic hedgehog pathway interfering compounds deviate from expression profiles of cyclopamine
Transcriptional responses of zebrafish embryos exposed to potential sonic hedgehog pathway interfering compounds deviate from expression profiles of cyclopamine
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DOI：
10.1016/j.reprotox.2011.12.010
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发表时间：
2012-04-01
影响因子：
3.3
通讯作者：
Scholz, Stefan
中科院分区：
文献类型：
--
作者：
Buettner, Anita;Busch, Wibke;Scholz, Stefan
两个小分子，SANT-2和GANT-61，可能干扰声波刺猬途径（Shh）的分子反应已在斑马鱼胚胎中通过微阵列分析进行了研究。对于这两种化合物和阳性参比环巴胺，先前对转录因子Gli 1的报告基因测定表明对hedgehog信号传导途径的抑制。在斑马鱼胚胎中，仅观察到环巴胺与Shh干扰相关的典型表型（cyclopia）。此外，只有环巴胺导致与刺猬信号特异性相关的基因的抑制，并证实了已发表的微阵列数据。与这些数据相反，hspb 11被另外鉴定为暴露于环巴胺的最显著的下调基因。SANT-2或GANT-61分别对基因表达模式没有或产生不同的影响。细胞报告和斑马鱼胚胎测定和潜在的影响，识别干扰特定发育途径的化合物之间的差异的原因进行了讨论。(C)2012 Elsevier Inc. All rights reserved.
The molecular responses of two small molecules, SANT-2 and GANT-61, potentially interfering with the sonic hedgehog pathway (Shh) have been studied in zebrafish embryos by microarray analysis. For both compounds and the positive reference cyclopamine previous reporter gene assays for the transcription factor Gli1 have indicated an inhibition of the hedgehog signaling pathway. In zebrafish embryos a typical phenotype (cyclopia) associated with Shh interference was only observed for cyclopamine. Furthermore, only cyclopamine led to the repression of genes specifically associated with hedgehog signaling and confirmed published microarray data. In contrast to these data hspb11 was additionally identified as the most pronounced down-regulated genes for exposure to cyclopamine. No or different effects on gene expression patterns were provoked by SANT-2 or GANT-61, respectively. Reasons for the discrepancies between cellular reporter and the zebrafish embryo assay and potential implications for the identification of compounds interfering with specific developmental pathways are discussed. (C) 2012 Elsevier Inc. All rights reserved.