Bangi Erdem, Garza Dan, Hild Marc
J Chem Biol. 2011 Apr;4(2):55-68. doi: 10.1007/s12154-010-0051-5. Epub 2010 Dec 22.
The recent establishment of high-throughput methods for culturing Drosophila provided a unique ability to screen compound libraries against complex disease phenotypes in the context of whole animals. However, as compound studies in Drosophila have been limited so far, the degree of conservation of compound activity between Drosophila and vertebrates or the effectiveness of feeding as a compound delivery system is not well known. Our comprehensive in vivo analysis of 27 small molecules targeting seven signaling pathways in Drosophila revealed a high degree of conservation of compound activity between Drosophila and vertebrates. We also investigated the mechanism of action of AY9944, one of the Hh pathway antagonists that we identified in our compound feeding experiments. Our epistasis analysis of AY9944 provided novel insights into AY9944's mechanism of action and revealed a novel role for cholesterol transport in Hh signal transduction.
The online version of this article (doi:10.1007/s12154-010-0051-5) contains supplementary material, which is available to authorized users.
最近建立的用于培养果蝇的高通量方法提供了一种独特的能力，即在全动物的背景下针对复杂疾病表型筛选化合物文库。然而，由于迄今为止果蝇中的化合物研究有限，果蝇与脊椎动物之间化合物活性的保守程度或作为化合物递送系统的喂食有效性尚不清楚。我们对果蝇中针对七条信号通路的27种小分子进行的全面体内分析表明，果蝇与脊椎动物之间化合物活性具有高度保守性。我们还研究了AY9944的作用机制，AY9944是我们在化合物喂食实验中鉴定出的Hh通路拮抗剂之一。我们对AY9944的上位性分析为AY9944的作用机制提供了新的见解，并揭示了胆固醇转运在Hh信号转导中的新作用。
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