7.013 4.6.07PowerPoint PresentationSlide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 3115.11Formation IIIMorphogenesis: building 3D structures7.0134.6.07STARTSTARTFOUNDATIOFOUNDATIONSNSHow-to 1How-to 1FORMATIOFORMATIONNHow-to 2How-to 2SYSTEMSYSTEMSSPROBLEMSPROBLEMSBIOCHEM GENETICS CELL BIO.MOL. BIOSTEM CELLS,CLONINGREC. DNAPOSITION&FATE 3DSTRUCTURESTEPSVIRUSESCANCERHUMANDISEASELIFELIFENERVOUSIMMUNESYSTEMSBIOLOGYFUTUREFUTUREDorsal determinationSee Purves 20.3Egg-catenin - phosphorylated- unstable, cytoplasmicDVDV2-4 cells and older:- determinants inhibit -catenin phosph.- dorsally stable, nuclear20H. Sive MIT 2007determinantMesoderm determinationHILONodal (ligand) gradientanimal polevegetal pole2 - 500+ cellsmesodermLow Nodal induces mesoderm500+ cells(High Nodal induces endoderm)22H. Sive MIT 2007Nodal binds receptor thatactivates Smad2 txn factorNodal ligand+DV-cateninDorsal500+ cellslow NodalMesoderm500+ cellsanimal polevegetal pole23H. Sive MIT 2007dorsal mesoderm:-cat + low Nodal(Smad2)activates MyoDtranscription=Dorsal mesoderm = future muscle4,000+ cell stageSomites: Segments that will form muscle, skeleton and skinQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.Biological 3D structuresQuickTime™ and aPhoto - JPEG decompressorare needed to see this picture.Specialized cell shape:neuron1QuickTime™ and aPhoto - JPEG decompressorare needed to see this picture.QuickTime™ and aPhoto - JPEG decompressorare needed to see this picture.Organ: kidney2QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.Lab Grows Bladders From Cells of PatientsWashington PostTuesday, April 4, 2006 3QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.Stages in Xenopus developmentegg (0hpf)early blastula (4hpf)late blastula (8hpf)neurula (16hpf) tadpole (40h)differentiation QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.gastrula (11hpf)movementdivision, determination4H. Sive MIT 2007first structuresPile of cells (blastula)3D structure(organ)What processes would turn the pile of cells into a 3D structure? (about 6)5QuickTime™ and aPhoto - JPEG decompressorare needed to see this picture.Cell sorting due to differential and homotypic cell adhesion (N-Cadherin vs E-cadherin)6Epidermal cellsEpidermal cellsEpidermal cellsEpidermal cellsNeural plate cellsCell dissociationReaggregationCell typesortingEpidermal cellsOutsideNeural insideEpithelium:cell sheetextracellularmatrix (ECM)apicalbasalMesenchyme: single cellsEpithelium/mesenchyme and transitionjunctionsH. Sive MIT 20077Shape and movement:role of cytoskeletonG-actinunpolymerized F-actinpolymerized Platelets changing shape during clottingresting clottingFrom Molecular Biology of the Cell/ Lodish89From Molecular Cell Biology/ LodishZone of actin polymerizationFront/leading edgeDirection ofmovementnucleusRear/trailingedgeLamellipodia/filopodiaActin polymerization during cell movementRearrangement of microfilaments (F-actin) with cell movementQuickTime™ and aPhoto decompressorare needed to see this picture.10cellsReceptors connect ECM and cytoskeletonSee Purves 4.26receptorscytoskeletonECM proteinsproteoglycansAdhesion receptors: integrinsECM proteins: collagen, laminin, fibronectin11H. Sive MIT 2007Front (leading edge)increased adhesionRear (trailing edge)adhesion lossF-actinECMreceptorligandfocal adhesionnucmovementCell adhesion and signaling12H. Sive MIT 2007ligand (laminin) binds receptor (integrin) which activates Focal Adhesion Kinaseactivates GTPase (rac/cdc42/rho)activates profilin which increases F-actinEpithelial sheets andbuilding tubesCell shape changesvia cytoskeletoncuboidalcolumnarwedgedFlat epithelial sheetBent epithelial sheetsquamous13apicalbasalEpithelial sheets can roll or bend to form a tubeExamples: brain, spinal cord14Amphibian neural tube forms by rolling up an epithelial sheetQuickTime™ and aMotion JPEG B decompressorare needed to see this picture.15Ray KellerMesenchymal cells can condense to form a tubeExamples: blood vessels, some kidney tubules16Purves 48.12:Lung tubules17Lung tubule branching: initial steps18An epithelial sheet can extend to form a tubeExample: primary tracheal tubules19Single cells can roll or hollow into tubesExamples: secondary and terminal tracheal tubules20epitheliumFGF (ligand)= branchlessFGF inhibitor = sproutygenesPrimary tracheal outgrowth and branching (Drosophila)See Purves 48.5FGF receptor = breathless21O2 stressPrimary tubule Secondary TerminalTubule morphogenesis in cultureQuickTime™ and aVideo decompressorare needed to see this picture.2215.11FGF = ligandReceptor (tyrosine kinase)Purves: 15.9: Fibroblast Growth Factor
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