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7.013 4.6.07

7.013 4.6.07. Formation III Morphogenesis: building 3D structures. SYSTEMS BIOLOGY. STEM CELLS, CLONING. LIFE. FUTURE. How-to 2. VIRUSES. 3D STRUCTURE. IMMUNE. NERVOUS. PROBLEMS. CANCER. POSITION &FATE. SYSTEMS. FORMATION. REC. DNA. How-to 1. HUMAN DISEASE. STEPS.

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7.013 4.6.07

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  1. 7.0134.6.07 Formation III Morphogenesis: building 3D structures

  2. SYSTEMS BIOLOGY STEM CELLS, CLONING LIFE FUTURE How-to 2 VIRUSES 3D STRUCTURE IMMUNE NERVOUS PROBLEMS CANCER POSITION &FATE SYSTEMS FORMATION REC. DNA How-to 1 HUMAN DISEASE STEPS BIOCHEM GENETICS MOL. BIO CELL BIO. START FOUNDATIONS

  3. H. Sive MIT 2007 20 Dorsal determination See Purves 20.3 D V • Egg • b-catenin • phosphorylated • unstable, cytoplasmic D V • 2-4 cells and older: • determinants inhibit b-catenin phosph. • dorsally stable, nuclear determinant

  4. H. Sive MIT 2007 500+ cells mesoderm Low Nodal induces mesoderm (High Nodal induces endoderm) 22 Nodal binds receptor that activates Smad2 txn factor animal pole 2 - 500+ cells LO HI vegetal pole Nodal (ligand) gradient Mesoderm determination Nodal ligand

  5. animal pole H. Sive MIT 2007 4,000+ cell stage dorsal mesoderm: b-cat + low Nodal (Smad2) activates MyoD transcription = Dorsal mesoderm = future muscle 23 500+ cells 500+ cells + low Nodal D V b-catenin Mesoderm Dorsal vegetal pole

  6. Somites: Segments that will form muscle, skeleton and skin

  7. Biological 3D structures

  8. 1 Specialized cell shape: neuron

  9. 2 Organ: kidney

  10. 3 Lab Grows Bladders From Cells of Patients Washington Post Tuesday, April 4, 2006

  11. H. Sive MIT 2007 4 egg (0hpf) late blastula (8hpf) early blastula (4hpf) division, determination Stages in Xenopus development gastrula (11hpf) movement neurula (16hpf) tadpole (40h) differentiation first structures

  12. 5 Pile of cells (blastula) 3D structure (organ) What processes would turn the pile of cells into a 3D structure? (about 6)

  13. 6 Epidermal cells Epidermal cells Epidermal cells Epidermal cells Cell type sorting Reaggregation Cell dissociation Neural plate cells Epidermal cells Outside Neural inside Cell sorting due to differential and homotypic cell adhesion (N-Cadherin vs E-cadherin)

  14. Mesenchyme: single cells 7 Epithelium/mesenchyme and transition apical Epithelium: cell sheet junctions basal extracellular matrix (ECM) H. Sive MIT 2007

  15. Shape and movement: role of cytoskeleton

  16. 8 Platelets changing shape during clotting resting clotting G-actin unpolymerized F-actin polymerized From Molecular Biology of the Cell/ Lodish

  17. 9 Actin polymerization during cell movement Zone of actin polymerization Front/ leading edge nucleus Direction of movement Rear/ trailing edge Lamellipodia/filopodia From Molecular Cell Biology/ Lodish

  18. 10 Rearrangement of microfilaments (F-actin) with cell movement

  19. 11 receptors Adhesion receptors: integrins ECM proteins: collagen, laminin, fibronectin See Purves 4.26 Receptors connect ECM and cytoskeleton cells cytoskeleton ECM proteins proteoglycans H. Sive MIT 2007

  20. 12 ligand(laminin) binds receptor(integrin) which activates Focal AdhesionKinase activates GTPase(rac/cdc42/rho) activates profilin whichincreases F-actin Cell adhesion and signaling Rear (trailing edge) adhesion loss Front (leading edge) increased adhesion F-actin nuc receptor ECM ligand focal adhesion movement H. Sive MIT 2007

  21. Epithelial sheets and building tubes

  22. apical 13 columnar cuboidal squamous wedged basal Cell shape changes via cytoskeleton Flat epithelial sheet Bent epithelial sheet

  23. 14 Epithelial sheets can roll or bend to form a tube Examples: brain, spinal cord

  24. 15 Ray Keller Amphibian neural tube forms by rolling up an epithelial sheet

  25. 16 Mesenchymal cells can condense to form a tube Examples: blood vessels, some kidney tubules

  26. 17 Purves 48.12: Lung tubules

  27. 18 Lung tubule branching: initial steps

  28. 19 An epithelial sheet can extend to form a tube Example: primary tracheal tubules

  29. 20 Single cells can roll or hollow into tubes Examples: secondary and terminal tracheal tubules

  30. FGF inhibitor = sprouty FGF (ligand)= branchless FGF receptor = breathless 21 epithelium Primary tubule Secondary Terminal O2 stress genes Primary tracheal outgrowth and branching (Drosophila) See Purves 48.5

  31. 22 Tubule morphogenesis in culture

  32. 23 FGF = ligand 15.11 Receptor (tyrosine kinase) Purves: 15.9: Fibroblast Growth Factor signaling

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