Functional Genomic Analysis of C. elegans Molting 英文参考文献.docVIP

o Openaccess,freelyavailableonline PL S BIOLOGY FunctionalGenomicAnalysis ofC.elegansMolting Alison R.Frand, Sascha Russel, Gary Ruvkun* Department ofMolecular Biology, Massachusetts General Hospital,Boston, Massachusetts, United States ofAmerica, and Genetics Department, Harvard MedicalSchool, Boston,Massachusetts,UnitedStatesofAmerica Althoughthemoltingcycleisahallmarkofinsectsandnematodes,neithertheendocrinecontrolofmoltingviasize, stage, and nutritional inputs nor the enzymatic mechanism for synthesis and release of the exoskeleton is well understood. Here,we identify endocrineand enzymatic regulators ofmolting in C.elegans through agenome-wide RNA-interference screen. Products of the 159 genes discovered include annotated transcription factors, secreted peptides,transmembraneproteins,andextracellularmatrixenzymesessentialformolting.Fusionsbetweenseveral genesandgreenfluorescentproteinshowapulseofexpressionbeforeeachmoltinepithelialcellsthatsynthesizethe exoskeleton,indicatingthatthecorrespondingproteinsaremadeinthecorrecttimeandplacetoregulatemolting.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 genesareconservedin parasitic nematodesresponsiblefor humandisease, andthusrepresent attractivetargetsforpesticideandpharmaceuticaldevelopment. Citation:FrandAR,RusselS,RuvkunG(2005)FunctionalgenomicanalysisofC.elegansmolting.PLoSBiol3(10):e312 elegansrequirescholesterol,thebiosyntheticprecursor ofall steroid hormones, as well as the low-density lipoprotein Introduction Ecdysozoan animals, including nematodes and arthropods [1], develop through periodic larval stage molts when the exoskeletonisshedandsynthesizedanew.Althoughmolting is the hallmark of the most abundant and diverse group of animals on the planet, including a wide variety of human pests and pathoge