V动物身体图式的模式建成I

DevelopmentalBiologyPatterningthebodyplaninanimals--invertebratesPatternformationisoneoftheessentialprinciplesofdevelopment(I)Morphogenesisisthedevelopmentalprocessofformingthetissue,organandembryo.Forexample,embryogenesisistheprocessbywhichtheembryowithawell-orderedspatialarrangementsofdifferentiatedtissuesandorgansisformed.Morphogenesisinvolvesacombinationofcellproliferation,differentiation,movement,adhesionandinduction.However,thequestionofhowthismorphogenesishappensisreallyaboutpatternformation（模式建成）.Patternformationistheprocessofdevelopingaprogrammeorblueprintforconstructingtheembryos.Itinitiallyinvolveslayingdowntheoverallbodyplan（身体图式）-definingthemainbodyaxesoftheembryosothatthehead(anterior)andtail(posterior)ends,andtheback(dorsal)andunderside(ventral)arespecified.Themainbodyaxesaretheantero-posterioraxis,whichrunsfromtheheadtothetail,andthedorso-ventralaxis,runningfromthebacktothebelly.Thesetwoaxesareatrightanglestoeachother.Whilethebodyaxesarespecified,theembryoispatternedalongboththeantero-posterior,anddorso-ventralaxes.So,patternformationisbasicallycomprisedofthebodyaxesspecification/formation,andpatterningalongthebodyaxes.Differentspeciesspecifythebodyaxesatdifferenttimes,usingdifferentmechanisms.Patternformationisoneoftheessentialprinciplesofdevelopment(II)Patterningthebodyplaninanimals1DevelopmentoftheDrosophilabodyplan1.1Specificationoftheantero-posterioranddorso-ventralaxisinDrosophilaoocyte1.2SettingupthebodyaxesinDrosophila1.3PatterningtheDrosophilaembryo2Patterningthevertebratebodyplan2.1Settingupthebodyaxesinamphibians(Xenopus)2.2Somiteformationandantero-posteriorpatterning2.3PatterningthevertebratenervoussystemPatterningthebodyplaninanimals1DevelopmentoftheDrosophilabodyplan1.1Specificationoftheantero-posterioranddorso-ventralaxisinDrosophilaoocyte1.2SettingupthebodyaxesinDrosophila1.3PatterningtheDrosophilaembryo2Patterningthevertebratebodyplan2.1Settingupthebodyaxesinamphibians(Xenopus)2.2Somiteformationandantero-posteriorpatterning2.3PatterningthevertebratenervoussystemPatterningoftheDrosophilaembryoalongthebodyaxesThebodyaxesarespecifiedinthedevelopingoocyteThebodyaxesarefullyestablishedintheveryearlyembryoAsthedevelopmentproceeds,theembryoispatternedalongthetwoaxes:thatistodividetheembryointodistinctregionsalongbothaxesPatterningthebodyplaninanimals1DevelopmentoftheDrosophilabodyplan1.1Specificationoftheantero-posterioranddorso-ventralaxisinDrosophilaoocyte1.2SettingupthebodyaxesinDrosophila1.3PatterningtheDrosophilaembryo2Patterningthevertebratebodyplan2.1Settingupthebodyaxesinamphibians(Xenopus)2.2Somiteformationandantero-posteriorpatterning2.3PatterningthevertebratenervoussystemTheDrosophilafemalereproductivesystemEggdevelopmentinDrosophilaEggdevelopmentinDrosophilaOverviewoftheDrosophilaoogenesisDrosophilabodyaxesarespecifiedintheoocyteduringoogenesisTheantero-posterioraxisoftheDrosophilaoocyteisspecifiedbyinteractionsoftheoocytewiththeposteriorfolliclecellsduringmid-oogenesis.Thedorso-ventralaxisoftheoocyteisspecifiedbymovementoftheoocytenucleusfollowedbysignalingbetweenoocyteandthesurroundingfolliclecells(卵泡细胞).Mechanismsunderlyingspecificationoftheantero-posterioranddorso-ventralaxesinDrosophilaoocyteWhenafollicle/eggchamberleavesthegermarium,theoocyteisalwaysfoundatthemostposteriorpositioninthegerm-linecyst.Thisposteriorpositioningoftheoocyteplaysakeyroleinspecificationoftheantero-posterioranddorso-ventralaxesintheoocyteduringmid-oogenesis.Theantero-posterioranddorso-ventralaxesoftheoocytearespecifiedduringmid-oogenesisthroughreciprocalsignalingbetweentheoocyteandthesurroundingepithelialfolliclecells.TheposteriorpositioningoftheoocyteinthenascenteggchamberplayakeyroleinspecificationofthebodyaxesintheoocyteANotch/DeltaandJAK/Stat-dependentrelaymodelfortheoocytepositioningintheposteriorofeggchambersGermlinecellsofolderfollicleInductionofanteriorpolarcellsInductionofstalkUpregulationofDE-cadherinintheposteriorfolliclecellsandtheoocyteofyoungerfolliclePosterioroocytelocalizationinyoungerfollicleNotch/DeltaJAK/StatNotch/DeltaThebodyaxesarespecifiedduringmid-oogenesisthroughthereciprocalsignalingbetweentheoocyteandthesurroundingfolliclecellsThePFCssendbackaunknownsignaltooocyteActivationofproteinkinaseAinoocyteMicrotubulecytoskeletonreorganizationDyneinmovesthebicoidmRNAtotheanteriorendoftheeggKinesinImovestheoskarmRNAtotheposteriorendPatterningthebodyplaninanimals1DevelopmentoftheDrosophilabodyplan1.1Specificationoftheantero-posterioranddorso-ventralaxisinDrosophilaoocyte1.2SettingupthebodyaxesinDrosophila1.3PatterningtheDrosophilaembryo2Patterningthevertebratebodyplan2.1Settingupthebodyaxesinamphibians(Xenopus)2.2Somiteformationandantero-posteriorpatterning2.3PatterningthevertebratenervoussystemSettinguptheDrosophilabodyaxesThebodyaxesarealreadlyspecifiedintheDrosophilaegg,andbecomefullyestablishedandpatternedintheveryearlyembryowhileitisstillinthesyncytialblastoderm（合胞体胚盘）.Organizationalongtheantero-posterioranddorso-ventralaxesoftheearlyembryodevelopsmoreorlesssimultaneously,butissetupbyindependentmechanismsandbydifferentsetsofgenesineachaxis.PatterningoftheDrosophilaembryooccursalongthetwobodyaxes:thatistodividetheembryointodistinctregionsalongboththeantero-posterioranddorso-ventralaxes.Threeclassesofmaternalgenesareinvolvedinsettinguptheantero-posterioraxisintheveryearlyembryo(I)Atmid-oogenesis,theantero-posterioraxisisspecifiedintheeggbythelocalizeddistributionofthematernalgenemRNAs,suchasbicoidmRNAintheanterior,andoskarmRNAintheposterior.Uponfertilization,thesemRNAscanbetranslatedintoproteins.Attheanteriorpole,bicoidmRNAistranslatedintoBicoidprotein,whichdiffusesthroughouttheblastodermandformsaconcentrationgradientthatishighestattheanterior.Attheposteriorpole,thenanosmRNAinassociationwithOskarproteinistranslatedintoNanosprotein,formingagradientthatishighestattheposterior.Thus,thegradientsofthesematernalproteins(BicoidandNanos)determinetheantero-posterioraxisintheearlyembryo.Bicoidproteinformsanantero-posteriorconcentrationgradientintheearlyembryoToppanel:themRNAisvisualizedbyinsituhybridizationMiddlepanel:theBicoidproteinisstainedwithalabeledantibodyThebicoidgeneisnecessaryforthedevelopmentoftheanteriorstructuresThebicoidgeneisnecessaryforthedevelopmentoftheanteriorstructuresMutationsinnanosgeneleadtolackingalargepartoftheposteriorregion(abodomen)Amodelofantero-posterioraxisgeneratedbytheDrosophilamaternaleffectgenesInadditiontoBicoidandNanosproteins,thereisthirdsetofmaternalgeneswhoseproteinsgeneratetheextremitiesoftheantero-posterioraxis.Acriticalgenehereappearstobetorso,ageneencodingareceptortyrosinekinase(RTK).Threeclassesofmaternalgenesareinvolvedinsettinguptheantero-posterioraxisintheveryearlyembryo(II)Mutationsintorsogeneleadtolackingthestructuresattheextremeendsoftheantero-posterioraxis,acronandtelsonWhileandaftertheantero-posterioranddorso-ventralaxesareestablishedintheveryearlyembryo,patterningoftheembryooccursalongthebodyaxes.Alongtheantero-posterioraxistheembryobecomesdividedintoseveralbroadregions,whichwillbecomethehead,thorax,andabdomenofthelarvaandadult.Typically,thethoraxandabdomenbecomedividedintosegmentsastheembryodevelops.Eachsegmenthasitsownuniquecharacter,asrevealedbyitsexternalcuticularstructures.TheembryoispatternedalongtheAPaxisthroughthecontrolofdifferentsetsofzygoticgeneexpressionbythematernalgenesTherelationshipbetweenparasegmentsandsegmentsintheearlyembryo,lateembryo,andadultflyT1:legsonlyT2:wingsandlegsT3:halteresandlegsComparisonoflarvalandadultsegmentationinDrosophilaThethreethoracicsegmentscanbedistinguishedbytheirappendagesTheNobelprizeinphysiology&medicinein1995wasawardedto3developmentalbiologistsfortheirworkinthegeneticcontroloftheearlyembryonicdevelopmentinDrosophilaChristianeNüsslein-VolhardEricF.WieschausEdwardB.LewisThesequentialexpressionofdifferentsetsofzygoticgenespatternsthebodyplanalongtheAPaxisSegmentpolaritygenesHomeoticselectorgenesBicoid---anteriormorphogen(Theproteingradientfromyellowtored)Hunchback/Kruppel---gapgeneprotein(Orange:thedomainofHunchbackexpressiononly;Green:thedomainofKruppelexpression;Yellow:overlapbetweenHunchbackandKruppel)FushiTarazu---pair-rulegeneproteinEngrailed---segmentpolaritygeneproteinThetemporalandspatialexpressionofthosematernalandzygoticgenescontrolsthepatterningoftheembryoalongtheAPaxisSpecificationoftheidentity(characteristicstrucutre)ofeachsegmentisaccomplishedbythehomeoticselectorgenesTheAntennapediacomplexlabandDfd---theheadsegmentsScrandAntp---thethoracicsegmentsTheBithoraxcomplexUbx---thethirdthoracicsegmentAbdAandAbdB---theabdominalsegmentsLoss-of-functionmutationsintheUltrabithoraxgenecantransformthe3rdthoracicsegmentintoanother2ndthoracicsegment,producingafour-wingedflyEctopicexpressionofAntennapediageneintheheadleadstolegsratherthanantennaegrowingoutoftheheadsocketsWildtypeMutant1stand2ndthoracicsegments3rdthoracicsegmentsandabdominalsegmentsThebodyaxesarespecifiedduringmid-oogenesisthroughthereciprocalsignalingbetweentheoocyteandthesurroundingfolliclecellsThegurkenmRNAanditsproteinarelocalizedbetweentheoocyteandthedorsalfolliclecellsoftheovaryThegurkenmRNATheGurkenproteinTheGurkenproteinTheactinSchematicrepresentationofthegenerationofdorsal-ventralaxisinDrosophilaembryoPipe:aheparansulfatesulfotransferase;Pelle:aproteinkinasePipeexpressiononlyinventralfolliclecellsActivationofTollsignalingpathwayinventralsideofearlyembryosTranslocationofDorsalproteintonucleusintheventralsideFormationofthenucleargradientofDorsalalongthedorsal-ventralaxisRoleoftheTollsignalingpathwayinpatterningoftheembryosalongtheDVaxisThedorso-ventralaxisisestablishedinearlyembryobytheintranuclearconcentrationgradientofDorsalproteinfromtheventraltodorsalTheembryoispatternedalongtheDVaxisthroughregulatingthezygoticgeneexpressionbythenucleargradientofDorsalproteinThedorso-ventralaxisoftheembryobecomesdividedintofourdistinctregionsearlyinembryogenesis:fromventraltodorsaltherearethemesoderm,whichwillformmusclesandotherinternalconnectivetissues;theventralectoderm,whichgivesrisetothelarvalnervoussystemandisthusalsocalledtheneurogenicectodermorneurectoderm;thedorsalectoderm,whichgivesrisetothelarvalepidermis;andtheamnioserosa,whichgivesrisetoanextra-embryonicmembraneonthedorsalsideoftheembryo.ThegradientofDorsalproteininthenucleisubdividestheembryoalongthedorso-ventralaxisthroughregulatingthezygoticgeneexpression.PatterningoftheDrosophilaembryoThebodyaxesarefullyestablishedintheveryearlyembryoAsthedevelopmentproceeds,theembryoispatternedalongthetwoaxes:thatistodividetheembryointodistinctregionsalongbothaxesThegeneticcontrolofpatterningoftheembryoalongtheDVaxisbythegradientofDorsalproteininthenuclusChangeinthenucleargradientofDorsalproteincancausedorsalizationorventralizationoftheembryoLoss-of-functionmutationsingenecactuscauseventralizationofthelarvaeTheventraldenticlebeltsincuticlepreparationofthewildtypeembryoLoss-of-functionmutationsingenecactuscauseventralizationofthelarvaeTheventraldenticlebeltsincuticlepreparationofthewildtypeembryoVentralizationphenotypeincactusmutantembryosSchematicrepresentationofthegenerationofdorsal-ventralaxisinDrosophilaembryoThesnakemutanteggsdevelopintothedorsalizedlarvaeThemutantlarvaconsistingentirelyofdorsalcellsRescueofthedorsalizationphenotypeinlarvaedevelopedfromsnakemutanteggsthatreceivedinjectionofmRNAfromwild-typeeggsLossoffunctionmutationsinlglproducealethalmalignanttumor-likephenotypeinDrosophilaDeLorenzoetal,1999lethal(2)giantlarvae(lgl)TheabsenceoflglgenefunctionblockstheeggdevelopmentatcertainstagesFusedeggchambersMultilayweredaccumulationoffollicularcellsatbothextremitiesofeggchambersThequestionremainstobeaddressedHowdoesLglfunctioninDrosophilaoogenesis?Mutationsinlglcauseoocytemispositioningintheeggchambera-OrbWTMutationsinlglcauseoocytemispositioningintheeggchambera-OrbWTlglts3/lgl4Thegermlinelglactivityisnotessentialfortheposteriorlocalizationoftheoocyteintheeggchambera-Orblgl4FRTcloneLglisrequiredinthefolliclecellstoregulatethecorrectpositioningoftheoocyteintheeggchambera-Orblgl4FRTcloneCoincidencebetweentheoocytemispositioningandtheeggchamberfusionswasobservedinlglmutantsa-Orblglts3/lgl4Coincidencebetweentheoocytemispositioningandtheeggchamberfusionswasobservedinlglmutantsa-Orblglts3/lgl4lgl4FRTcloneLglisrequiredforthestalkcelldifferentiationlinkedtotheoocytepositioningintheanterioradjacenteggchambera-Orba-BibWTLglisrequiredforthestalkcelldifferentiationlinkedtotheoocytepositioningintheanterioradjacenteggchambera-Orba-Biba-Orba-BibWTlgl4FRTcloneLglisrequiredforthestalkcelldifferentiationlinkedtotheoocytepositioningintheanterioradjacenteggchamberAnti-b-GalWTlgl4FRTclone93Freporter93FreporterLglisrequiredfortheinitialpositioningoftheoocyte,ratherjustforitsmaintenanceattheposteriorofthedevelopingeggchambersa-OrbWTLglisrequiredfortheinitialpositioningoftheoocyte,ratherjustforitsmaintenanceattheposteriorofthedevelopingeggchambersa-OrbWTlglts3/lgl4Lglisrequiredfortheinitialpositioningoftheoocyte,ratherjustforitsmaintenanceattheposteriorofthedevelopingeggchambersa-Orblglts3/lgl4WTlgl4FRTcloneLglfunctionsintheoocytepositioningbyaffectingtheDE-cadherinmediatedadhesionbetweenoocyteandposteriorfolliclecellsa-Arma-EglWTLglfunctionsintheoocytepositioningbyaffectingtheDE-cadherinmediatedadhesionbetweenoocyteandposteriorfolliclecellsa-Arma-EglWTlgl4FRTcloneSummary(I)LglisrequiredfortheestablishmentoftheinitialAPasymmetry.Loss-of-functionmutationsinlglcausemispositioningoftheoocyteintheanterioradjacentoneofthefusedeggchambers,duetolackofthestalkdifferentiation.Lglisrequiredfortheformationoftheoocytepolarityalongtheanteroposterior(AP)axisatmid-oogenesisa-StaufenWTLglisrequiredfortheformationoftheoocytepolarityalongtheanteroposterior(AP)axisatmid-oogenesisa-StaufenWTlgl4FRTcloneLglisrequiredfortheformationoftheoocytepolarityalongtheanteroposterior(AP)axisatmid-oogenesisa-Staufenlgl4FRTcloneWTlgl4FRTcloneLglisrequiredfortheformationoftheoocytepolarityalongthedorsoventral(DV)axisatmid-oogenesisa-GurkenWTLglisrequiredfortheformationoftheoocytepolarityalongthedorsoventral(DV)axisatmid-oogenesisa-GurkenWTlglts3/lgl4Lglisrequiredfortheformationoftheoocytepolarityalongthedorsoventral(DV)axisatmid-oogenesisa-GurkenWTlglts3/lgl4lgl4FRTcloneInactivationofLglcouldresultinafailuretoreorganizetheoocyteMTcytoskeletonatmid-oogenesisa-KinesinWTInactivationofLglcouldresultinafailuretoreorganizetheoocyteMTcytoskeletonatmid-oogenesisa-Kinesinlgl4FRTcloneWTInactivationofLglcouldresultinafailuretoreorganizetheoocyteMTcytoskeletonatmid-oogenesisa-KinesinWTlgl4FRTclonelgl4FRTcloneMutationsinLglintheposteriorfolliclecellsleadtodefectsindifferentiationofthosemutantcellsa-Fasciclin3WTMutationsinLglintheposteriorfolliclecellsleadtodefectsindifferentiationofthosemutantcellsa-Fasciclin3WTlgl4FRTcloneDefectiveposteriorfolliclecelldifferentiationisresponsiblefortheoocytepolarityphenotypeinlglmutantsAnti-b-GalWT998/12reporterAnti-b-GalDefectiveposteriorfolliclecelldifferentiationisresponsiblefortheoocytepolarityphenotypeinlglmutants998/12reporterWTlgl4FRTclone998/12reporterAnti-b-GalDefectiveposteriorfolliclecelldifferentiationisresponsiblefortheoocytepolarityphenotypeinlglmutantsWT998/12reporterlgl4FRTclone998/12reporter998/12reporterlgl4FRTcloneSummary(II)LglisrequiredfortheformationoftheoocytepolarityalongtheAPandDVaxesatmid-oogenesis.Removalofthelglgenefunctionfromtheposteriorfolliclecellsresultsinalossoftheoocytepolaritythatiselicitedbythefailureofthoseposteriorcellstodifferentiatenormally.Li,Q.,Xin,T.,Chen,W.,Zhu,M.,andLi,M.CellResearch.2008,18:372-384CurrentworkandfuturedirectionExplorethemechanismsunderlyingthedefectsindifferentiationofthestalkcellsandposteriorfolliclecellsinlglmutantsduringoogenesis:Notch/DeltasignalingJAK/STATsignalingEGFRsignaling