Repressor Dimerization in the Zebrafish Somitogenesis Clock 英文参考文献.docVIP

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Repressor Dimerization in the Zebrafish Somitogenesis Clock 英文参考文献.doc

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Repressor Dimerization in the Zebrafish Somitogenesis Clock 英文参考文献

RepressorDimerizationintheZebrafish SomitogenesisClock Olivier Cinquin1,2,3¤* 1CentreforMathematicsandPhysicsintheLifeSciencesandExperimentalBiology,UniversityCollegeLondon,London,UnitedKingdom,2DepartmentofAnatomyand Developmental Biology, University College London, London, United Kingdom, 3 Laboratoire TIMC-IMAG, Centre national de la recherche scientifique, Universite′ Joseph Fourier,Faculte′ deMe′decine,LaTronche,France Theoscillationsofthesomitogenesisclockarelinkedtothefundamentalprocessofvertebrateembryosegmentation, yetlittleisknownabouttheirgeneration.Inzebrafish,ithasbeenproposedthatHerproteinsrepressthetranscription oftheirownmRNA.However,initssimplestform,thismodelisincompatiblewiththefactthatmorpholinoknockdown of Her proteins can impair expression of their mRNA. Simple self-repression models also do not account for the spatiotemporalpatternofgeneexpression,withwavesofgeneexpressionshrinkingastheypropagate.Herewestudy computationallythenetworksgeneratedbythewealthofdimerizationpossibilitiesamongsttranscriptionalrepressors inthezebrafishsomitogenesisclock.Thesenetworkscanreproduceknockdownphenotypes,andstronglysuggestthe existence of a Her1–Her7 heterodimer, so far untested experimentally. The networks are the first reported to reproducethespatiotemporalpatternofthezebrafishsomitogenesisclock;theyshednewlightontheroleofHer13.2, the only known link between the somitogenesis clock and positional information in the paraxial mesoderm. The networks can also account for perturbations of the clock by manipulation of FGF signaling. Achieving an understanding of the interplay between clock oscillations and positional information is a crucial first step in the investigationofthesegmentationmechanism. Citation:CinquinO(2007)Repressordimerizationinthezebrafishsomitogenesisclock.PLoSComputBiol3(2):e32.doi:10.1371/journal.pcbi.0030032 expression of her1, her7, and deltaC. her1 and her7 share a common 12-kb promoter [2], which contains nine copies of Introduction A