生物技术-发育生物学-12届课件 I 发育生物学概论

DevelopmentalBiology生命学院李明发生命药学大楼2#-519Tel:34204918,mfli@Reference(I)-TextbooksPrinciplesofDevelopment

(thethirdedition),

editedby

LewisWolpert

DevelopmentalBiology(theninthedition),editedbyScottF.Gilbert发育生物学原理,樊启昶、白书农编著

Reference(II)-Academic

journalsCell,Nature,Science,PNAS,CurrentBiologyetcGenes&Development,DevelopmentalCell,DevelopmentDevelopmentalBiology,BMCDevelopmentalBiology,MechanismsofDevelopment,DevelopmentalDynamicsetcPlantCell,PlantJournal,PlantPhysiologyetcThecontentsofdevelopmentalbiologyChapter1:TheintroductionofdevelopmentalbiologyChapter2:Developmentalsignalingpathways Chapter3:ThegermcelldevelopmentandfertilizationChapter4:EarlyembryonicdevelopmentChapter5:DevelopmentofthebodyplaninanimalsChapter6:OrganogenesisChapter7:PlantdevelopmentChapter8:StemcellbiologyDevelopmentalBiologyChapter1:TheintroductionofdevelopmentalbiologyTheintroductionofdevelopmentalbiology(I)1Basicconcepts&Scope2Thequestionsofdevelopmentalbiology2.1Twofundamentalquestions2.2Sixgeneralquestions3Essentialprinciplesofdevelopment3.1Cellproliferation&Programmedcelldeath3.2Cellfatedeterminationanddifferentiation3.3Cellinduction3.4Cellrecognitionandadhesion3.5Changeincellshape&Cellmovements/migration3.6Patternformation&MorphogenesisTobecontinuedTheintroductionofdevelopmentalbiology(II)4Modelorganismsfordevelopmentalbiology4.1Invertebrates4.2Vertebrates4.3PlantsConceptsandscopeofdevelopmentalbiology

Thedisciplineofdevelopmentalbiologyarisesfromembryology.Thestudyofdevelopmentalbiology,however,goeswellbeyondthedevelopmentoftheembryo.

germcelldevelopment

fertilizedegg embryogenesis post-embryonicdevelopment Ageingandsenescence

Understandingthegeneticcontrolofthosedevelopmentalprocessesisoneofmainthemesofdevelopmentalbiology.Questionsofdevelopmentalbiology(I)Twofundamentalquestions:

Howdoesthefertilizedegggiverisetotheadultbody? Howdoesthatadultbodyproduceyetanotherbody?Questionsofdevelopmentalbiology(II)Sixgeneralquestions:

Differentiation: Howcanthefertilizedegggeneratehundredsofdifferentcelltypes?

Morphogenesis: Howcanthedifferentiatedcellsformtheorderedandintricatetissues andorgans?

(celldivision,migration,shapechange,adhesion,death, patternformationetc)

Growth：

Howisorgansizecontrolled?Howdoourcellsknowwhentostop dividing?

Questionsofdevelopmentalbiology(III)

Reproduction:

Howarethegermcellssetaparttoformthenextgeneration?

Evolutionanddevelopment:

Manydevelopmentalprocessesandmechanisms(signalingpathways, Hoxgenes)atthecellularandmolecularlevelhavebeenconserved amongdistantlyrelatedorganisms. Theevolutionofmulticellularformsoflifeistheresultofinherited

changesindevelopment.Thosechangesindevelopmentmakenew individualstobetteradapttotheirenviroments.Howdochangesin developmentcreatenewbodyforms?

Questionsofdevelopmentalbiology(IV)

Environmentalintegration:

Howisthedevelopmentofanorganismintegratedintothelarger contextofitshabitat?

Sexdeterminationinreptiles

(temperature)

Wingcolorsincertainbutterflies(temperature,daylight) Environmenthasamuchgreaterimpactonplantdevelopmentthanon thatofanimals Whatpropertiesenablescertainchemicalstoalterdevelopment?

EssentialprinciplesofdevelopmentCellproliferation&ProgrammedcelldeathCellfatedetermination&differentiationCellinductionCellrecognition&adhesionChangeincellshape&CellmovementsPatternformation&MorphogenesisEssentialprinciplesofdevelopmentCellproliferation&Programmedcelldeath

Cellfatedetermination&differentiationCellinductionCellrecognition&adhesionChangeincellshape&CellmovementsPatternformation&MorphogenesisCellproliferation&programmedcelldeathisessentialforembryogenesisandorganogenesis

Cellproliferationbeginsinthecleavageofthefertilizedeggandfunctionsthroughoutdevelopmentofthemulticellularorganisms.Themechanismsunderlyingcellproliferationindevelopmentisnotfullyunderstood(growthfactor,growthhormoneetc).

Cellproliferationisaccompaniedbyprogressivecellfatedetermination/differentiationindevelopment

Programmedcelldeathisrequiredfordevelopmentofcertaintissuesandorgans,e.g

thedigitformationinvertebratelimbs

thecavityformationintheepiblast(innercellmass)ofthemouse embryo

developmentofthevertebratenervoussystem(eliminationofexcess neurons (e.g,50%ofthemotorneurons)forsculptingproper functionalconnectionsbetweenneuronsandtheirtargets)

RegulationofthelimbapoptosisbyBMPsGremlin:aninhibitorofBMPsInhibitionofBMPsignalingcanleadtothewebbingofchicklimbsthroughblockingtheapoptosisinthespacebetweenthedigitsEssentialprinciplesofdevelopment

Cellproliferation&ProgrammedcelldeathCellfatedetermination&differentiation

CellinductionCellrecognition&adhesionChangeincellshape&CellmovementsPatternformation&MorphogenesisCellfatedetermination&Celldifferentiation

Cellfatedetermination&Celldifferentiationareessentialforembryogenesisandorganogenesis.Embryogenesisisaprocessofprogressivecellfatedeterminationanddifferentiation.

Cellfatedeterminationisinitiatedatlatestageofthecleavage,andextendsovercleavageandgastrulation.Theunderlyingmechanismsneedtobeaddressed.

unevendistributionofthecellfatedeterminantsinasymmetriccelldivision

cell-cellinteractions(cellinduction)Cellfatedetermination&Celldifferentiation

Celldifferentiationisaccompaniedwithcellproliferationthroughoutembryogenesisandorganogenesis.

Generally,

celldifferentiationisirreversible,butthedifferentiatedcellscanbereprogrammed.

Dedifferentiation(去分化):

Thecloningofanimals

iPSCs(inducedpluripotentcells,诱导性多能干细胞)

Transdifferentiation

(转分化):

InterchangebetweendifferentcelltypesThestateofdeterminationofcellsatanydevelopmentalstagecanbedemonstratedbytransplantationexperimentsAsymmetriccelldivisioncanmakecellsdifferentfromeachotherviaunequaldistributionofthecellfatedeterminants

InductiveinteractionscanmakecellsdifferentfromeachotherEssentialprinciplesofdevelopment

Cellproliferation&ProgrammedcelldeathCellfatedetermination&differentiationCellinduction

Cellrecognition&adhesionChangeincellshape&CellmovementsPatternformation&MorphogenesisInduction(Proximateinteraction)

Induction:Onecell,ortissuedirectsthedevelopmentofanother,neighboringcellortissue.Thephenomenonofinductionplaysadecisiveroleinorganogenesis.

Thereareatleast2componentstoeveryinductiveinteraction.

Inducer:thecell/tissuethatproducesasignal(orsignals)

Responder:thetissuerespondingtoaspecificsignal(competence)

Thefeaturesofinduction:

Reciprocalinductions

Sequentialinductiveevents

Inductioncanoccuronthecell-celllevel.

InductionrequiresbothproperinducerandresponderTheopticvesicleisabletoinducelensformationintheanteriorportionoftheectoderminXenopusTheschematicdiagramoftheinductionofthemouseembryonicopticstructure

day9

day10day11day13Cascadesofinduction:Reciprocalandsequentialinductiveevents

FGF8istheinductivesignalforinducinglensformationinthedevelopingchickeyeFGF8istheinductivesignalforinducinglensformationinthedevelopingchickeyeL-Maf

isamarkeroflenstissuedifferentiationInsituhybridizationshowingtheexpressionofthePax6geneinthedevelopingmouseeyeThePax6geneisexpressedinboththepresumptivelensectodermandtheopticcupThePax6proteinappearstobeimportantininductionofopticstructureinthedevelopingmammalianeyeRoleofPax6intheinductionofopticandnasalstructuresintheratembryoA:

WildtyperatembryoB:HomozygousPax6mutantC:

Newborn

wildtyperatD:HomozygousPax6mutantPax6isneededforthesurfaceectodermtorespondtotheinductivesignalfromtheopticvesicle;theinducingtissuedoesnotneeditEssentialprinciplesofdevelopment

Cellproliferation&ProgrammedcelldeathCellfatedetermination&differentiationCellinductionCellrecognition&adhesion

Changeincellshape&CellmovementsPatternformation&MorphogenesisCellrecognition&adhesion

Cellrecognition&adhesionplayanimportantroleinorganizationoftissuesandorgansindevelopment.

Theadhesionofcellstoeachotherandtotheextracellularmatrixmaintainstheintegrityoftissues,andtheboundariesbetweendifferenttissuesandstructures.

Theadhesionofcellstoeachotherisdeterminedbythecell-adhesionmoleculesthatarelocalizedoncellsurface.

3classesofadhesionmoleculesareimportantindevelopment:

Cadherins:E-cadherin,N-cadherinandP-cadherin

Immunoglobulinsuperfamily

IntegrinsThereexistdifferencesincelladhesivenessindifferenttissuesDifferentialadhesivenessbetweencellsdependsonthekindsandnumbersofadhesionmoleculesoncellsurfaceEssentialprinciplesofdevelopment

Cellproliferation&ProgrammedcelldeathCellfatedetemination&differentiationCellinductionCellrecognition&adhesionChangeincellshape&Cellmovements

Patternformation&MorphogenesisChangeincellshape&Cellmovements/migration

Cellsactivelyundergomajorchangesinshapeduringdevelopment.Changesincellshapeareassociatedwithcellmovements(e.g.cellmigration,infoldingofepithelialsheetsatneurulation,invaginationofendodermalormesodermalcellsatgastrulation

).

Changesincellshape&cellmovementsaregeneratedbythecytoskeletonrearrangements(microfilaments,microtubules,andintermediatefilaments).

Theyareimportantinmorphogenesisandorganogenesis:

Formationoftheneuraltubeinvertebrates Tissuemovementduringgastrulation DevelopmentofgonadsAftertheirformationduringgastrulation,theprimordialgermcellsinmouseembryosmigratetothegonadsEssentialprinciplesofdevelopment

Cellproliferation&ProgrammedcelldeathCellfatedetemination&differentiationCellinductionCellrecognition&adhesionChangeincellshape&CellmovementsPatternformation&MorphogenesisPatternformation&Morphogenesis

Morphogenesisisthedevelopmentalprocessofchangeinforminthedevelopingembryo,involvesacombinationofcellproliferation,differentiation,movement,adhesionandinduction.

Thequestionofhowthismorphogenesishappensisreallyaboutpatternformation(模式建成).

Patternformationistheprocessofdevelopingaprogrammeorblueprintforconstructingtheembryos.

Patternformationinitiallyinvolveslayingdowntheoverallbodyplan（身体图式）---definingthemainbodyaxesoftheembryosothatthehead(anterior)andtail(posterior),andback(dorsal)andunderside(ventral)arespecified.

TheembryonicchickwingModelorganismsforstudyingdevelopment

Therearegeneralprinciplesofdevelopmentthatapplytoallanimals.Genesfunctioninginembryogenesisarehighlyconservedfromtheinvertebratestovertebrates.

So,arelativelysmallnumberofanimalsarechosenasmodelorganisms,originallybecausetheyareamenableto

experimentalmanipulationorgeneticanalysis

Eachspecieshasitsadvantagesanddisadvantagesasadevelopmentalmodel

Modelorganismsforstudyingdevelopment

Invertebrates

ThenematodewormCaenorhaditis

elegans

ThefruitflyDrosophila

Vertebrates

ThefrogXenopus

Thechicken

Thezebrafish

Themouse

Plants

Arabidopsisthaliana

Suitabilityforgeneticanalysis;about19,000genesinthegenome

Formationofeachcellcanbeobserved

It’ssmallnumberofcells:558in1stlarvae;959inadultInvariantcelllineage