Functional genomic analysis of C. elegans molting.
Functional genomic analysis of C. elegans molting.
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DOI：
10.1371/journal.pbio.0030312
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发表时间：
2005-10
期刊：
影响因子：
9.8
通讯作者：
Ruvkun G
中科院分区：
文献类型：
--
作者：
Frand AR;Russel S;Ruvkun G
虽然蜕皮周期是昆虫和线虫的标志，但通过大小、阶段和营养输入对蜕皮的内分泌控制以及外骨骼合成和释放的酶促机制都没有很好的理解。在这里，我们确定内分泌和酶调节蜕皮在C。elegans通过全基因组RNA干扰筛选。所发现的159个基因的产物包括注释的转录因子、分泌肽、跨膜蛋白和蜕皮所必需的细胞外基质酶。几个基因和绿色荧光蛋白之间的融合在每次蜕皮前在合成外骨骼的上皮细胞中显示出脉冲式的表达，这表明相应的蛋白质是在正确的时间和地点产生的，以调节蜕皮。我们进一步表明，特定基因的失活废除的绿色荧光蛋白报告基因的表达，揭示调控网络，可能会夫妇的蜕皮内分泌线索所必需的基因的表达。许多蜕皮基因在引起人类疾病的寄生线虫中是保守的，因此代表了农药和药物开发的有吸引力的靶标。作者使用全基因组RNA干扰筛选来鉴定和表征与C。elegans elegans蜕皮他们调查了涉及蜕皮的监管网络，为这个复杂的过程提供了重要的新见解。
Although the molting cycle is a hallmark of insects and nematodes, neither the endocrine control of molting via size, stage, and nutritional inputs nor the enzymatic mechanism for synthesis and release of the exoskeleton is well understood. Here, we identify endocrine and enzymatic regulators of molting in C. elegans through a genome-wide RNA-interference screen. Products of the 159 genes discovered include annotated transcription factors, secreted peptides, transmembrane proteins, and extracellular matrix enzymes essential for molting. Fusions between several genes and green fluorescent protein show a pulse of expression before each molt in epithelial cells that synthesize the exoskeleton, indicating that the corresponding proteins are made in the correct time and place to regulate molting. We show further that inactivation of particular genes abrogates expression of the green fluorescent protein reporter genes, revealing regulatory networks that might couple the expression of genes essential for molting to endocrine cues. Many molting genes are conserved in parasitic nematodes responsible for human disease, and thus represent attractive targets for pesticide and pharmaceutical development. The authors use a genome-wide RNA-interference screen to identify and characterize genes involved in C. elegans molting. They investigate regulatory networks involved in molting, lending important new insights into this complex process.
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