V动物身体图式的模式建成I课件

DevelopmentalBiologyPatterningthebodyplaninanimals--invertebratesPatternformationisoneoftheessentialprinciplesofdevelopment(I)

Morphogenesisisthedevelopmentalprocessofformingthetissue,organandembryo.Forexample,embryogenesisistheprocessbywhichtheembryowitha

well-orderedspatialarrangementsofdifferentiatedtissuesandorgansisformed.

Morphogenesisinvolvesacombinationofcellproliferation,differentiation,movement,adhesionandinduction.

However,thequestionofhowthismorphogenesishappensisreallyaboutpatternformation（模式建成）.

Patternformationistheprocessofdevelopingaprogrammeorblueprintforconstructingtheembryos.Itinitiallyinvolveslayingdowntheoverall

body

plan

（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:thatistodividetheembryointodistinctregionsalongbothaxesTheDrosophilafemalereproductivesystemEggdevelopmentinDrosophilaEggdevelopmentinDrosophilaDrosophilabodyaxesarespecifiedintheoocyteduringoogenesis

Theantero-posterioraxisoftheDrosophilaoocyteisspecifiedbyinteractionsoftheoocytewiththeposteriorfolliclecellsduringmid-oogenesis.

Thedorso-ventralaxisoftheoocyteisspecifiedbymovementoftheoocytenucleusfollowedbysignalingbetweenoocyteandthesurroundingfolliclecells(卵泡细胞).Mechanismsunderlyingspecificationoftheantero-posterioranddorso-ventralaxesinDrosophilaoocyte

Whenafollicle/eggchamberleavesthegermarium,theoocyteisalwaysfoundatthemostposteriorposition

inthegerm-linecyst.Thisposteriorpositioningoftheoocyteplaysakeyroleinspecificationoftheantero-posterioranddorso-ventralaxesintheoocyteduringmid-oogenesis.

Theantero-posterioranddorso-ventralaxes

oftheoocytearespecifiedduringmid-oogenesisthroughreciprocalsignalingbetweentheoocyteandthesurroundingepithelialfolliclecells.Theposteriorpositioningoftheoocyteinthenascenteggchamberplayakeyroleinspecificationofthebodyaxesintheoocyte

Thebodyaxesarespecifiedduringmid-oogenesisthroughthereciprocalsignalingbetweentheoocyteandthesurroundingfolliclecellsThePFCssendbackaunknownsignaltooocyte

ActivationofproteinkinaseAinoocyte

Microtubulecytoskeletonreorganization

DyneinmovesthebicoidmRNAtotheanteriorendoftheeggKinesinImovestheoskarmRNAtotheposteriorend

SettinguptheDrosophilabodyaxes

ThebodyaxesarealreadlyspecifiedintheDrosophilaegg,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.Atthe

posteriorpole,thenanosmRNAinassociationwithOskarproteinistranslatedintoNanosprotein,formingagradientthatishighestattheposterior.Thus,thegradientsofthesematernalproteins(BicoidandNanos)determinetheantero-posterioraxisintheearlyembryo.Bicoidproteinformsanantero-posteriorconcentrationgradientintheearlyembryoToppanel:

themRNAisvisualizedbyinsituhybridizationMiddlepanel:theBicoidproteinisstainedwithalabeledantibodyThebicoidgeneisnecessaryforthedevelopmentoftheanteriorstructuresMutationsinnanosgeneleadtolackingalargepartoftheposteriorregion(abodomen)Mutationsintorsogeneleadtolackingthestructuresattheextremeendsoftheantero-posterioraxis,acronandtelson

Whileandaftertheantero-posterioranddorso-ventralaxesareestablishedintheveryearlyembryo,patterningoftheembryooccursalongthebodyaxes.

Alongtheantero-posterioraxistheembryobecomesdividedintoseveralbroadregions,whichwillbecomethehead,thorax,andabdomenofthelarvaandadult.Typically,thethoraxandabdomenbecomedividedintosegmentsastheembryodevelops.Eachsegmenthasitsownuniquecharacter,asrevealedbyitsexternalcuticularstructures.

TheembryoispatternedalongtheAPaxisthroughthecontrolofdifferentsetsofzygoticgeneexpressionbythematernalgenesTherelationshipbetweenparasegmentsandsegmentsintheearlyembryo,lateembryo,andadultflyT1:legsonlyT2:wingsandlegsT3:halteresandlegsComparisonoflarvalandadultsegmentationinDrosophilaThethreethoracicsegmentscanbedistinguishedbytheirappendagesTheNobelprizeinphysiology&medicinein1995wasawardedto3developmentalbiologistsfortheirworkinthegeneticcontroloftheearlyembryonicdevelopmentinDrosophilaChristianeNüsslein-Volhard

EricF.Wieschaus

EdwardB.Lewis

ThesequentialexpressionofdifferentsetsofzygoticgenespatternsthebodyplanalongtheAPaxisSegmentpolaritygenesHomeoticselectorgenesBicoid---anteriormorphogen(Theproteingradientfromyellowtored)Hunchback/Kruppel---gapgeneprotein(Orange:thedomainofHunchbackexpressiononly;Green:thedomainofKruppelexpression;Yellow:overlapbetweenHunchbackandKruppel)

FushiTarazu---pair-rulegeneproteinEngrailed---segmentpolaritygeneproteinThetemporalandspatialexpressionofthosematernalandzygoticgenescontrolsthepatterningoftheembryoalongtheAPaxisSpecificationoftheidentity(characteristicstrucutre)ofeachsegmentisaccomplishedbythehomeoticselectorgenesTheAntennapediacomplexlabandDfd---theheadsegmentsScrandAntp---thethoracicsegmentsTheBithoraxcomplexUbx

---thethirdthoracicsegmentAbdAandAbdB---theabdominalsegmentsLoss-of-functionmutationsintheUltrabithoraxgenecantransformthe3rdthoracicsegmentintoanother2ndthoracicsegment,producingafour-wingedflyEctopicexpressionofAntennapediageneintheheadleadstolegsratherthanantennaegrowingoutoftheheadsocketsWildtypeMutant1stand2ndthoracicsegments3rdthoracicsegmentsandabdominalsegments

Thebodyaxesarespecifiedduringmid-oogenesisthroughthereciprocalsignalingbetweentheoocyteandthesurroundingfolliclecellsThegurkenmRNAanditsproteinarelocalizedbetweentheoocyteandthedorsalfolliclecellsoftheovaryThegurkenmRNATheGurkenproteinThe

GurkenproteinTheactinSchematicrepresentationofthegenerationofdorsal-ventralaxisinDrosophilaembryoPipe:aheparansulfatesulfotransferase;Pelle:aproteinkinasePipeexpressiononlyinventralfolliclecellsActivationofTollsignalingpathwayinventralsideofearlyembryosTranslocationofDorsalproteintonucleusintheventralsideFormationofthenucleargradientofDorsalalongthedorsal-ventralaxisRoleoftheTollsignalingpathwayinpatterningoftheembryosalongtheDVaxisThedorso-ventralaxisisestablishedinearlyembryobytheintranuclearconcentrationgradientofDorsalproteinfromtheventraltodorsal

TheembryoispatternedalongtheDVaxisthroughregulatingthezygoticgeneexpressionbythenucleargradientofDorsalprotein

Thedorso-ventralaxisoftheembryobecomesdividedintofourdistinctregionsearlyinembryogenesis:fromventraltodorsaltherearethemesoderm,whichwillformmusclesandotherinternalconnectivetissues;theventralectoderm,whichgivesrisetothelarvalnervoussystemandisthusalsocalledtheneurogenicectodermorneurectoderm;thedorsalectoderm,whichgivesrisetothelarvalepidermis;andtheamnioserosa,whichgivesrisetoanextra-embryonicmembraneonthedorsalsideoftheembryo.

ThegradientofDorsalproteininthenucleisubdividestheembryoalongthedorso-ventralaxisthroughregulatingthezygoticgeneexpression.PatterningoftheDrosophilaembryoThebodyaxesarefullyestablishedintheveryearlyembryoAsthedevelopmentproceeds,theembryoispatternedalongthetwoaxes:thatistodividetheembryointodistinctregionsalongbothaxes

ThegeneticcontrolofpatterningoftheembryoalongtheDVaxisbythegradientofDorsalproteininthenuclusChangeinthenucleargradientofDorsalproteincancausedorsalizationorventralizationoftheembryoLoss-of-functionmutationsingenecactuscauseventralizationofthelarvaeTheventraldenticlebeltsincuticlepreparationofthewildtypeembryoLoss-of-functionmutationsingenecactuscauseventralizationofthelarvaeTheventraldenticlebeltsincuticlepreparationofthewildtypeembryoVentralizationphenotypeincactusmutantembryosSchematicrepresentationofthegenerationofdorsal-ventralaxisinDrosophilaembryoThesnakemutanteggsdevelopintothedorsalizedlarvaeThemutantlarvaconsistingentirelyofdorsalcellsRescueofthedorsalizationphenotypeinlarvaedevelopedfromsnakemutanteggsthatreceivedinjectionofmRNAfromwild-typeeggsLossoffunctionmutationsinlglproducealethalmalignanttumor-likephenotypeinDrosophilaDeLorenzoetal,1999lethal(2)giantlarvae(lgl)TheabsenceoflglgenefunctionblockstheeggdevelopmentatcertainstagesFusedeggchambersMultilayweredaccumulationoffollicularcellsatbothextremitiesofeggchambersThequestionremainstobeaddressedHowdoesLglfunctioninDrosophilaoogenesis?Mutationsinlglcauseoocytemispositioningintheeggchamber

a-OrbWTMutationsinlglcauseoocytemispositioningintheeggchamber

a-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-KinesinWTInactivat