Formation IIIMorphogenesis: building 3D structures7.0134.6.07STARTSTARTFOUNDATIONSFOUNDATIONSHow-to 1How-to 1FORMATIONFORMATIONHow-to 2How-to 2SYSTEMSSYSTEMSPROBLEMSPROBLEMSBIOCHEM 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 stage Somites:Segments that will form muscle, skeleton and skinBiological 3D structuresSpecialized cell shape:neuron1Organ: kidney2Lab Grows Bladders From Cells of PatientsWashington PostTuesday, April 4, 2006 3Stages in Xenopus developmentegg (0hpf)early blastula (4hpf)late blastula (8hpf)neurula (16hpf) tadpole (40h)differentiation 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)5Cell 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 transitionjunctions H. 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 movement10cellsReceptors 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 byrolling up an epithelial sheet15Ray 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 culture2215.11FGF = ligandReceptor (tyrosine kinase)Purves: 15.9: Fibroblast Growth Factor
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