胚层发育和器官系统培训课件

胚层发育和器官系统Theembryonicchickwing2胚层发育和器官系统Thevertebratelimbdevelopmentisaparticularlygoodsysteminwhichtostudypatternformationduringorganogenesis(I)

Thevertebratelimbisacomplexorganwiththreedevelopmentalaxes:theproximo-distalaxisrunningfromthebaseofthelimbtothetip,theantero-posterioraxisrunningparallelwiththebodyAPaxis,andthedorso-ventralaxisrunningfromthebackofthehandtothepalm.

Thus,thelimbdevelopmentisaparticularlygoodsysteminwhichtostudypatternformation

Sincethelimbs,unlikeheartorbrain,arenotessentialforembryoniclife,onecanexperimentallyremoveortransplantpartsofthedevelopinglimb,orcreatelimb-specificmutantswithoutinterferingwiththevitalprocessesoftheorganism.Thisisgoodadvantageofstudyingpatternformationinorganogenesis

3胚层发育和器官系统Thevertebratelimbdevelopmentisaparticularlygoodsysteminwhichtostudypatternformationduringorganogenesis(II)

Thelimbisagoodmodelforstudyingcellularinteractionswithinastructurecontainingalargenumberofcells,andforelucidatingtheroleofintercellularsignalingindevelopment.Recently,particularsignalproteinshavebeenidentifiedtofunctioninpatterningalongeachofthreelimbaxes:

FGFfamilyinPr-Daxialpatterning

Sonichedgehog(Shh)proteininA-Paxialpatterning

Wnt7ainD-Vaxialpatterning

4胚层发育和器官系统Thevertebratelimbdevelopsfromalimbbud5胚层发育和器官系统3Thelimbdevelopment3.1Specificationandformationofthelimbbud3.2Thelimboutgrowthandgenerationoftheproximal-distalaxis3.3Theanterior-posterioraxialpatterning3.4Patterningthedorsal-ventralaxis3.5Coordinatingthethreeaxes3.6DevelopmentofthedigitsDevelopmentofthevertebratelimb6胚层发育和器官系统3Thelimbdevelopment3.1Specificationandformationofthelimbbud3.2Thelimboutgrowthandgenerationoftheproximal-distalaxis3.3Theanterior-posterioraxialpatterning3.4Patterningthedorsal-ventralaxis3.5Coordinatingthethreeaxes3.6DevelopmentofthedigitsDevelopmentofthevertebratelimb7胚层发育和器官系统Thevertebratelimbdevelopsfromalimbbud8胚层发育和器官系统ProliferationofmesodermalcellsfromthelateralplatemesodermcausesthelimbbudtobulgeoutwardWhilethelateralplatemesodermalcellsgeneratetheskeletalelementsofthelimb,cellsfromthesomitesprovidethelimb’smusculature9胚层发育和器官系统10胚层发育和器官系统FGF10secretedfromthelateralplatemesodermcellsisthesignalforlimbbudinductionA:FGF10becomesexpressedinthelateralplatemesoderm

ofthelimbbud-formingregionB:EctopicexpressionofFGF10beneaththeflankectoderminducesextralimbFGF10Ectopiclimb11胚层发育和器官系统FGF10initiatesthelimbbud-forminginteractionsbetweentheectodermandthemesodermviadualsignalinginductionA:FGF10isoriginallyexpressedthroughoutthelateralplatemesodermB:FGF10becomesrestrictedtothelimbbud-formingregions,controlledbyWnt2bandWnt8crespectivelyC:DualinductionbetweenFGF10inthemesodermandFGF8intheapicalectodermridge(AER)Molecular

modelfortheinitiationofthelimbbudinthechickbetween48and54hoursofgestation12胚层发育和器官系统3Thelimbdevelopment3.1Specificationandformationofthelimbbud3.2Thelimboutgrowthandgenerationoftheproximal-distalaxis3.3Theanterior-posterioraxialpatterning3.4Patterningthedorsal-ventralaxis3.5Coordinatingthethreeaxes3.6DevelopmentofthedigitsDevelopmentofthevertebratelimb13胚层发育和器官系统14胚层发育和器官系统Apicalectodermalridge(AER)Progresszone(PZ)15胚层发育和器官系统TheAERisrequiredforboththeoutgrowthoflimbandthecorrectproximo-distalpatterning16胚层发育和器官系统FGF8isexpressedintheapicalectodermalridge(AER)17胚层发育和器官系统FGF8canfunctionallysubstitutefortheAERThesimilarresultscanbeobtainedwithFGF4,indicatingthatFGF8/FGF4arekeysignalsfortheAER18胚层发育和器官系统Themesenchymecells:

induceandsustaintheAER,anddeterminethetypeoflimbtobeformed.TheAER:

amajorsignalingcenterforthedevelopinglimb,andmaintainsthemesenchymeinaproliferatingphasethatenablesthePr-DgrowthofthelimbTheproximal-distalgrowthofthelimbbudinvolvesinteractionsbetweentheAERandtheunderlyingmesenchyme19胚层发育和器官系统

RoleoftheAERorthePZ(progresszone)inspecifyingtheproximal-distalaxis?

ThemechamismsunderlyingthePDaxisspecificationandpatterning?Howisdevelopmentoftheproximal-distalaxisaccomplishedduringthelimboutgrowth?20胚层发育和器官系统Specificationofproximal-distalaxisiscontrolledbytheprogresszonemesenchyme,rathertheAER(I)OlderAERcombinedwithyoungermesodermgeneratesnormallimbs,ratherproducinglimbswithdeletionsinthemiddle.YoungerAERcombinedwitholdermesodermgeneratesnormallimbs,ratherproducingduplicationsofstructures.ThefollowingtwotransplantationexperimentsdidnotsupportthenotionthattheAERspecifiestheproxiomal-distalaxisofthedevelopinglimbs.21胚层发育和器官系统Anearlywing-budprogresszonewastransplantedtoalatewingbudthathadalrealyformedulnaandradiusAlatewing-budprogresszonewastransplantedtoanearlywingbudExtraproximalstructureLackofintermediatestructuresSpecificationofproximal-distalaxisiscontrolledbytheprogresszonemesenchyme,rathertheAER(II)22胚层发育和器官系统TwoproposedmodelsforthemesodermalspecificationofthePr-Daxisofthelimb

a:thetimingmechanism,thecellfate

beingdeterminedbyhowlong

theyremainintheprogresszoneb:predeterminationinearlybud23胚层发育和器官系统HoxgenesspecifythePr-Daxisofthelimb24胚层发育和器官系统HoxgenesspecifythePr-DaxisofthelimbLossoffunctionmutationsinHoxa-11andHoxd-11

leadtolackingtheulnaandradiusoftheforelimbs

Humansynpolydactyly(manyfingersjoinedtogether)syndromeresultsfromhomozygosityforamutationattheHoxd-13loci25胚层发育和器官系统3Thelimbdevelopment3.1Specificationandformationofthelimbbud3.2Thelimboutgrowthandgenerationoftheproximal-distalaxis3.3Theanterior-posterioraxialpatterning3.4Patterningthedorsal-ventralaxis3.5Coordinatingthethreeaxes3.6Developmentofthedigits

Developmentofthevertebratelimb26胚层发育和器官系统Zoneofpolarizingactivity(ZPA)canspecifythelimbpatternalongtheanterior-posterioraxisThezoneofpolarizingactivity(ZPA)intheposteriorlimbbudhasorganizingpropertiesthatarealmostasstrikingasthoseoftheSpemannorganizerinamphibians27胚层发育和器官系统Sonichedgehog(Shh)isexpressedintheZPAShhShh28胚层发育和器官系统ThemolecularbasisforspecificationofZPAFGF8intheAERinducesthemesenchymeexpressingthetranscriptionfactorsHoxb-8anddHANDtoexpressShh,therebyformingtheZPAintheposteriorregionoflimbbud30胚层发育和器官系统Sonichedgehogformsamorphogengradientthatspecifiespatternalongthelimb’santerior-posterioraxis31胚层发育和器官系统3Thelimbdevelopment3.1Specificationandformationofthelimbbud3.2Thelimboutgrowthandgenerationoftheproximal-distalaxis3.3Theanterior-posterioraxialpatterning3.4Patterningthedorsal-ventralaxis3.5Coordinatingthethreeaxes3.6Developmentofthedigits

Developmentofthevertebratelimb32胚层发育和器官系统Thedorsal-ventralpolarityofthelimbbudisdeterminedbytheectodermencasingit

Iftheectodermisrotated180withrespecttothelimbbudmesenchyme,thedorsal-ventralaxisispartiallyreversed.

TheWnt7ageneisspecificallyexpressedinthedorsal(butnotventral)ectodermofchickandmouselimbbuds,suggestingaroleofWnt7ainspecifyingdorsal-ventralpolarity.33胚层发育和器官系统LossofWnt7afunctionleadstodisruptionofthedorsal-ventralpatterningofthelimbVt:theventraltendons（肌腱）Vp:theventralfootpad（脚垫））A:WildtypeembryonicmouseforelimbpawB:ThemicedeficientforWnt7agene34胚层发育和器官系统ThemolecularmechanismsunderlyingtheWnt7a-mediatedDVpatterningofthelimbWnt7ainducesactivationoftheLmx1geneinthedorsalmesenchyme.Lmx1gene

encodesatranscriptionfactorthatappearstobeessentialforspecifyingdorsalcellfatesinthelimbSpatialexpressionofWnt7ainthedorsalectodermisregulatedbyengrailedgeneintheventralectoderm.35胚层发育和器官系统3Thelimbdevelopment3.1Specificationandformationofthelimbbud3.2Thelimboutgrowthandgenerationoftheproximal-distalaxis3.3Theanterior-posterioraxialpatterning3.4Patterningthedorsal-ventralaxis3.5Coordinatingthethreeaxes3.6DevelopmentofthedigitsDevelopmentofthevertebratelimb36胚层发育和器官系统Molecularinteractionsthatcoordinatelimbgrowthandpatterningalongthethreelimbaxes

37胚层发育和器官系统3Thelimbdevelopment