Ancestral Regulatory Circuits Governing Ectoderm Patterning Downstream of Nodal and BMP24 Revealed by Gene Regulatory Network Analysis in an Echinoderm 英文参考文献.docVIP

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Ancestral Regulatory Circuits Governing Ectoderm Patterning Downstream of Nodal and BMP24 Revealed by Gene Regulatory Network Analysis in an Echinoderm 英文参考文献.doc

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Ancestral Regulatory Circuits Governing Ectoderm Patterning Downstream of Nodal and BMP24 Revealed by Gene Regulatory Network Analysis in an Echinoderm 英文参考文献

AncestralRegulatoryCircuitsGoverningEctoderm PatterningDownstreamofNodalandBMP2/4Revealed byGeneRegulatoryNetworkAnalysisinanEchinoderm AlexandraSaudemont1.,EmmanuelHaillot1.,FlavienMekpoh1,NathalieBessodes1,MagaliQuirin1, Franc?oisLapraz1,Ve′roniqueDuboc1,EricRo¨ttinger1,RyanRange1,ArnaudOisel1,LydiaBesnardeau1, PatrickWincker2,ThierryLepage1* 1UMR 7009 CNRS, Universite′ de Pierre et Marie Curie (Paris 6), Observatoire Oceanologique, Villefranche-sur-Mer, France, 2Ge′noscope (CEA), UMR8030, CNRS and Universite′ d’Evry,Evry,France Abstract Echinoderms,whicharephylogeneticallyrelatedtovertebratesandproducelargenumbersoftransparentembryosthat can be experimentally manipulated, offer many advantages for the analysis of the gene regulatory networks (GRN) regulatinggermlayerformation.Duringdevelopmentoftheseaurchinembryo,theectodermisthesourceofsignalsthat patternallthreegermlayersalongthedorsal-ventralaxis.Howthissignalingcentercontrolspatterningandmorphogenesis oftheembryoisnotunderstood.Here,wereportalarge-scaleanalysisoftheGRNdeployedinresponsetotheactivityof thissignalingcenterintheembryosoftheMediterraneanseaurchinParacentrotuslividus,inwhichstudieswithhighspatial resolutionarepossible.Byusingacombinationofinsituhybridizationscreening,overexpressionofmRNA,recombinant ligand treatments, and morpholino-based loss-of-function studies, we identified a cohort of transcription factors and signalingmoleculesexpressedintheventralectoderm,dorsalectoderm,andinterposedneurogenic(‘‘ciliaryband’’)region inresponsetotheknownkeysignalingmoleculesNodalandBMP2/4anddefinedtheepistaticrelationshipsbetweenthe mostimportantgenes.TheresultantGRNshowedanumberofstrikingfeatures.First,Nodalwasfoundtobeessentialfor theexpressionofallventralanddorsalmarkergenes,andBMP2/4foralldorsalgenes.Second,goosecoidwasidentifiedasa central player in a regulatory sub-circuit controlling mouth formation, while tbx2/3 emerged as a critical factor for differentiationofthedorsalectoderm.Finally,andunexpect