Bài giảng Biology - Chapter 21: The Genetic Basis of Development

Chapter 21The Genetic Basis of DevelopmentOverview: From Single Cell to Multicellular OrganismThe application of genetic analysis and DNA technology Has revolutionized the study of developmentResearchersUse mutations to deduce developmental pathwaysHave applied the concepts and tools of molecular genetics to the study of developmental biologyFigure 21.1When the primary research goal is to understand broad biological principlesThe organism chosen for study is called a model organismFigure 21.2DROSOPHILA MELANOGASTER(FRUIT FLY)CAENORHABDITIS ELEGANS(NEMATODE)0.25 mmMUS MUSCULUS(MOUSE)DANIO RERIO(ZEBRAFISH)ARABIDOPSIS THAMANA(COMMON WALL CRESS)Concept 21.1: Embryonic development involves cell division, cell differentiation, and morphogenesisIn the embryonic development of most organismsA single-celled zygote gives rise to cells of many different types, each with a different structure and corresponding functionThe transformation from a zygote into an organismResults from three interrelated processes: cell division, cell differentiation, and morphogenesisFigure 21.3a, b(a) Fertilized eggs of a frog(b) Tadpole hatching from eggThrough a succession of mitotic cell divisionsThe zygote gives rise to a large number of cellsIn cell differentiationCells become specialized in structure and functionMorphogenesis encompasses the processesThat give shape to the organism and its various partsThe three processes of development overlap in timeFigure 21.4a, bAnimal development. Most animals go through some variation of the blastula and gastrula stages. The blastula is a sphere of cells surrounding a fluid-filled cavity. The gastrulaforms when a region of the blastula folds inward, creating a tube—a rudimentary gut. Once the animal is mature, differentiation occurs in only a limited way—for the replacement of damaged or lost cells.Plant development. In plants with seeds, a complete embryo develops within the seed. Morphogenesis, which involves cell division and cell wall expansion rather than cell or tissue movement, occurs throughout the plant’s lifetime. Apical meristems (purple) continuously arise and develop into the various plant organs as the plant grows to an indeterminate size.Zygote(fertilized egg)Eight cellsBlastula(cross section) Gastrula(cross section)Adult animal(sea star)CellmovementGutCell divisionMorphogenesisObservable cell differentiationSeedleavesShootapicalmeristemRootapicalmeristemPlantEmbryoinside seedTwo cells Zygote(fertilized egg)(a)(b)Concept 21.2: Different cell types result from differential gene expression in cells with the same DNADifferences between cells in a multicellular organismCome almost entirely from differences in gene expression, not from differences in the cells’ genomesEvidence for Genomic EquivalenceMany experiments support the conclusion thatNearly all the cells of an organism have genomic equivalence, that is, they have the same genesTotipotency in PlantsOne experimental approach for testing genomic equivalenceIs to see whether a differentiated cell can generate a whole organismEXPERIMENTTransversesection ofcarrot root2-mgfragmentsFragments cul-tured in nutrientmedium; stir-ring causessingle cells toshear off intoliquid.Single cellsfree insuspensionbegin todivide.Embryonicplant developsfrom a culturedsingle cell.Plantlet is cul-tured on agarmedium. Laterit is plantedin soil.RESULTS A singleSomatic (nonreproductive) carrotcell developed into a mature carrotplant. The new plant was a genetic duplicate(clone) of the parent plant.Adult plantCONCLUSION At least some differentiated (somatic) cells in plants are toipotent, ableto reverse their differentiation and then give rise to all the cell types in a mature plant.Figure 21.5A totipotent cellIs one capable of generating a complete new organismCloningIs using one or more somatic cells from a multicellular organism to make another genetically identical individualNuclear Transplantation in AnimalsIn nuclear transplantationThe nucleus of an unfertilized egg cell or zygote is replaced with the nucleus of a differentiated cellExperiments with frog embryosHave shown that a transplanted nucleus can often support normal development of the eggFigure 21.6EXPERIMENT Researchers enucleated frog egg cells by exposing them to ultraviolet light, which destroyed the nucleus. Nuclei from cells of embryos up to the tadpole stage were transplanted into the enucleated egg cells.Frog embryoFrog egg cellFrog tadpoleLess differ-entiated cellDonornucleustrans-plantedEnucleatedegg cellFully differ-entiated(intestinal) cellDonornucleustrans-plantedMost developinto tadpoles<2% developinto tadpolesRESULTS Most of the recipient eggs developed into tadpoles when the transplanted nuclei came from cells of an early embryo, which are relatively undifferentiated cells. But with nuclei from thefully differentiated intestinal cells of a tadpole, fewer than 2% of the eggs developed into normal tadpoles, and most of the embryos died at a much earlier developmental stage.CONCLUSION The nucleus from a differentiated frog cell can direct development of a tadpole. However, its ability to do so decreases as the donor cell becomes more differentiated, presumably because of changes in the nucleus.Reproductive Cloning of MammalsIn 1997, Scottish researchersCloned a lamb from an adult sheep by nuclear transplantationNucleusremovedMammarycell donorEgg celldonorEgg cellfrom ovaryCultured mammary cells are semistarved, arresting the cellcycle and causingdedifferentiationNucleus frommammary cellGrown in cultureEarly embryoImplanted in uterusof a third sheepSurrogatemotherEmbryonicdevelopmentLamb (“Dolly”)genetically identical to mammary cell donor456123Cells fusedAPPLICATION This method is used to produce cloned animals whose nuclear genes are identical to the donor animal supplying the nucleus.TECHNIQUE Shown here is the procedure used to produce Dolly, the first reported case of a mammal cloned using the nucleus of a differentiated cell.RESULTS The cloned animal is identical in appearance and genetic makeup to the donor animal supplying the nucleus, but differs from the egg cell donor and surrogate mother.NucleusremovedFigure 21.7“Copy Cat”Was the first cat ever clonedFigure 21.8Problems Associated with Animal CloningIn most nuclear transplantation studies performed thus farOnly a small percentage of cloned embryos develop normally to birthThe Stem Cells of AnimalsA stem cellIs a relatively unspecialized cell Can reproduce itself indefinitelyCan differentiate into specialized cells of one or more types, given appropriate conditionsFigure 21.9Early human embryoat blastocyst stage(mammalian equiva-lent of blastula)From bone marrowin this exampleTotipotentcellsPluripotentcellsCulturedstem cellsDifferentcultureconditionsDifferenttypes ofdifferentiatedcellsLiver cellsNerve cellsBlood cellsEmbryonic stem cellsAdult stem cellsStem cells can be isolated From early embryos at the blastocyst stageAdult stem cellsAre said to be pluripotent, able to give rise to multiple but not all cell typesTranscriptional Regulation of Gene Expression During DevelopmentCell determinationPrecedes differentiation and involves the expression of genes for tissue-specific proteinsTissue-specific proteinsEnable differentiated cells to carry out their specific tasksDNAOFFOFFOFFmRNAmRNAmRNAmRNAmRNAAnothertranscriptionfactorMyoDMuscle cell(fully differentiated)MyoD protein(transcriptionfactor)Myoblast (determined)Embryonicprecursor cellMyosin, othermuscle proteins,and cell-cycleblocking proteinsOther muscle-specific genesMaster control gene myoDNucleusDetermination. Signals from othercells lead to activation of a masterregulatory gene called myoD, andthe cell makes MyoD protein, atranscription factor. The cell, nowcalled a myoblast, is irreversiblycommitted to becoming a skeletalmuscle cell.1Differentiation. MyoD protein stimulatesthe myoD gene further, and activatesgenes encoding other muscle-specifictranscription factors, which in turn activate genes for muscle proteins. MyoD also turns on genes that block the cell cycle, thus stopping cell division. The nondividing myoblasts fuse to become mature multinucleate muscle cells, alsocalled muscle fibers.2Determination and differentiation of muscle cellsFigure 21.10Cytoplasmic Determinants and Cell-Cell Signals in Cell DifferentiationCytoplasmic determinants in the cytoplasm of the unfertilized eggRegulate the expression of genes in the zygote that affect the developmental fate of embryonic cellsSpermMolecules of another cyto-plasmic deter-minantFigure 21.11aUnfertilized egg cellMolecules of a a cytoplasmicdeterminantFertilizationZygote(fertilized egg)Mitotic cell divisionTwo-celledembryoCytoplasmic determinants in the egg. The unfertilized egg cell has molecules in its cytoplasm, encoded by the mother’s genes, that influence development. Many of these cytoplasmic determinants, like the two shown here, are unevenly distributed in the egg. After fertilization and mitotic division, the cell nuclei of the embryo are exposed to different sets of cytoplasmic determinants and, as a result, express different genes. (a)NucleusSpermIn the process called inductionSignal molecules from embryonic cells cause transcriptional changes in nearby target cellsFigure 21.11bEarly embryo(32 cells)NUCLEUSSignaltransductionpathwaySignalreceptorSignalmolecule(inducer)Induction by nearby cells. The cells at the bottom of the early embryo depicted here are releasing chemicals that signal nearby cells to change their gene expression.(b)Concept 21.3: Pattern formation in animals and plants results from similar genetic and cellular mechanismsPattern formationIs the development of a spatial organization of tissues and organsOccurs continually in plantsIs mostly limited to embryos and juveniles in animalsPositional informationConsists of molecular cues that control pattern formationTells a cell its location relative to the body’s axes and to other cellsDrosophila Development: A Cascade of Gene ActivationsPattern formationHas been extensively studied in the fruit fly Drosophila melanogasterThe Life Cycle of DrosophilaDrosophila developmentHas been well describedAfter fertilizationPositional information specifies the segmentsSequential gene expression produces regional differences in the formation of the segmentsKey developmental events in the life cycle of DrosophilaFigure 21.12Follicle cellNucleusEgg cellFertilizationNursecellEgg celldeveloping withinovarian follicleLaying of eggEggshellNucleusFertilized eggEmbryoMultinucleatesingle cellEarly blastodermPlasmamembraneformationLate blastodermCells ofembryoYolkSegmentedembryoBodysegments0.1 mmHatchingLarval stages (3)PupaMetamorphosisHeadThoraxAbdomen0.5 mmAdult flyDorsalAnteriorPosteriorVentralBODYAXES2134567Genetic Analysis of Early Development: Scientific InquiryThe study of developmental mutantsLaid the groundwork for understanding the mechanisms of developmentFigure 21.13EyeAntennaLeg Wild typeMutantAxis EstablishmentMaternal effect genesEncode for cytoplasmic determinants that initially establish the axes of the body of DrosophilaFlies with the bicoid mutationDo not develop a body axis correctlyHeadWild-type larvaTailTailMutant larva (bicoid)Drosophila larvae with wild-type and bicoid mutant phenotypes. A mutation in the mother’s bicoid gene leads to tail structures at both ends (bottom larva). The numbers refer to the thoracic and abdominal segments that are present.(a)T1T2T3A1A2A3A4A5A6A7A8A8A7A6A7A8TailFigure 21.14aTranslation of bicoid mRNAFertilizationNurse cellsEgg cellbicoid mRNADeveloping egg cellBicoid mRNA in mature unfertilized egg100 µmBicoid protein inearly embryoAnterior end(b) Gradients of bicoid mRNA and Bicoid protein in normal egg and early embryo.123Figure 21.14bSegmentation PatternSegmentation genesProduce proteins that direct formation of segments after the embryo’s major body axes are formedIdentity of Body PartsThe anatomical identity of Drosophila segmentsIs set by master regulatory genes called homeotic genesA summary of gene activity during Drosophila developmentHierarchy of Gene Activity in Early Drosophila DevelopmentMaternal effect genes (egg-polarity genes)Gap genesPair-rule genesSegment polarity genesHomeotic genes of the embryoOther genes of the embryoSegmentation genesof the embryoC. elegans: The Role of Cell SignalingThe complete cell lineage Of each cell in the nematode roundworm C. elegans is knownFigure 21.15ZygoteNervoussystem,outerskin, mus-culatureMusculature,gonadsOuter skin,nervous systemGerm line(futuregametes)MusculatureFirst cell divisionTime after fertilization (hours)010HatchingIntestineIntestineEggsVulvaANTERIORPOSTERIOR1.2 mmInductionAs early as the four-cell stage in C. elegansCell signaling helps direct daughter cells down the appropriate pathways, a process called inductionFigure 21.16a4AnteriorEMBRYOPosteriorReceptorSignalproteinSignalAnteriordaughtercell of 3Posteriordaughtercell of 3Will go on toform muscle and gonadsWill go on toform adultintestine12433Induction of the intestinal precursor cell at the four-cell stage.(a)Induction is also critical later in nematode development As the embryo passes through three larval stages prior to becoming an adultFigure 21.16bEpidermisGonadAnchor cellSignalproteinVulval precursor cellsInner vulvaOuter vulvaEpidermisADULTInduction of vulval cell types during larvaldevelopment.(b)An inducing signal produced by one cell in the embryoCan initiate a chain of inductions that results in the formation of a particular organProgrammed Cell Death (Apoptosis)In apoptosisCell signaling is involved in programmed cell death2 µmFigure 21.17In C. elegans, a protein in the outer mitochondrial membraneServes as a master regulator of apoptosis Ced-9protein (active)inhibits Ced-4activityMitochondrionDeathsignalreceptorCed-4Ced-3Inactive proteins(a) No death signalCed-9(inactive)CellformsblebsDeathsignalActiveCed-4ActiveCed-3ActivationcascadeOtherproteasesNucleases(b) Death signalFigure 21.18a, bIn vertebrates Apoptosis is essential for normal morphogenesis of hands and feet in humans and paws in other animalsFigure 21.19Interdigital tissue1 mmPlant Development: Cell Signaling and Transcriptional RegulationThanks to DNA technology and clues from animal researchPlant research is now progressing rapidlyMechanisms of Plant DevelopmentIn general, cell lineageIs much less important for pattern formation in plants than in animalsThe embryonic development of most plantsOccurs inside the seedPattern Formation in FlowersFloral meristemsContain three cell types that affect flower developmentFigure 21.20CarpelPetalStamenSepalAnatomy of a flowerFloral meristemTomato flowerCelllayersL1L2L3Tomato plants with a mutant alleleHave been studied in order to understand the genetic mechanisms behind flower developmentFigure 21.21Researchers grafted stems from mutant plants onto wild-type plants. They then planted the shoots that emerged near the graft site, many of which were chimeras.SepalPetalCarpelStamenWild-typenormalFasciated (ff)extra organsGraftChimerasFor each chimera, researchers recorded the flower phenotype: wild-type or fasciated. Analysis using other genetic markers identified the parental source for each of the three cell layers of the floral meristem (L1–L3) in the chimeras. Tomato plants with the fasciated (ff) mutation develop extra floral organs.EXPERIMENTRESULTSCONCLUSION The flowers of the chimeric plants had the fasciated phenotype only when the L3 layer came from the fasciated parent. Cells in the L3 layer induce the L1 and L2 layers to form flowers with a particular number of organs. (The nature of the inductive signal from L3 is not entirely understood.)Wild-type (ffFasciated (ffFloralmeristemL1L2L3KeyWild-typeparentPlantFlowerPhenotypeFloral MeristemChimera 1Chimera 2Chimera 3Wild-typeFasciatedFasciatedFasciatedWild-type))Fasciated (ffparent)Organ identity genesDetermine the type of structure that will grow from a meristemAre analogous to homeotic genes in animalsFigure 21.22Wild typeMutantConcept 21.4: Comparative studies help explain how the evolution of development leads to morphological diversityBiologists in the field of evolutionary developmental biology, or “evo-devo,” as it is often calledCompare developmental processes of different multicellular organismsWidespread Conservation of Developmental Genes Among AnimalsMolecular analysis of the homeotic genes in DrosophilaHas shown that they all include a sequence called a homeoboxAn identical or very similar nucleotide sequenceHas been discovered in the homeotic genes of both vertebrates and invertebratesFigure 21.23Adultfruit flyFruit fly embryo(10 hours)FlychromosomeMouse chromosomesMouse embryo(12 days)Adult mouseRelated genetic sequencesHave been found in regulatory genes of yeasts, plants, and even prokaryotesIn addition to developmental genesMany other genes involved in development are highly conserved from species to speciesIn some casesSmall changes in regulatory sequences of particular genes can lead to major changes in body form, as in crustaceans and insectsThoraxGenitalsegmentsAbdomenThoraxAbdomenFigure 21.24In other casesGenes with conserved sequences play different roles in the development of different speciesIn plantsHomeobox-containing genes do not function in pattern formation as they do in animalsComparison of Animal and Plant DevelopmentIn both plants and animalsDevelopment relies on a cascade of transcriptional regulators turning genes on or off in a finely tuned seriesBut the genes that direct analogous developmental processesDiffer considerably in sequence in plants and animals, as a result of their remote ancestry