LIFE Formation III. Morphogenesis: building 3D structures START FUTURE. How-to 2 PROBLEMS FORMATION SYSTEMS SYSTEMS.

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1 Formation III Morphogenesis: building 3D structures VIRUSES CANCER HUMAN DISEASE START SYSTEMS BIOLOGY PROBLEMS FUTURE LIFE IMMUNE NERVOUS SYSTEMS How-to 1 FOUNDATIONS How-to 2 REC. DNA BIOCHEM GENETICS MOL. BIO CELL BIO. STEM CELLS, CLONING FORMATION 3D STRUCTURE POSITION &FATE STEPS 20 Dorsal determination See Purves animal pole Nodal binds receptor that activates Smad2 txn factor V D cells 500+ cells LO mesoderm Egg!-catenin - phosphorylated - unstable, cytoplasmic determinant V 2-4 cells and older: - determinants inhibit!-catenin phosph. - dorsally stable, nuclear D HI vegetal pole Nodal (ligand) gradient Nodal ligand Mesoderm determination (High Nodal induces endoderm) Low Nodal induces mesoderm

2 23 animal pole 500+ cells 500+ cells V D + low Nodal!-catenin Dorsal vegetal pole 4,000+ cell stage = Dorsal mesoderm = future muscle Mesoderm dorsal mesoderm:!-cat + low Nodal (Smad2) activates MyoD transcription Somites: Segments that will form muscle, skeleton and skin 1 Biological 3D structures Specialized cell shape: neuron

3 2 3 Lab Grows Bladders From Cells of Patients Washington Post Tuesday, April 4, 2006 Organ: kidney 4 5 egg (0hpf) late blastula early blastula (8hpf) (4hpf) division, determination Stages in Xenopus development Pile of cells (blastula) gastrula (11hpf) movement neurula (16hpf) first structures tadpole (40h) differentiation 3D structure (organ) What processes would turn the pile of cells into a 3D structure? (about 6)

4 6 7 Epithelium/mesenchyme and transition Epidermal cells Cell dissociation Reaggregation Cell type sorting apical basal Epithelium: cell sheet junctions extracellular matrix (ECM) Neural plate cells Cell sorting due to differential and homotypic cell adhesion (N-Cadherin vs E-cadherin) Epidermal cells Outside Neural inside Mesenchyme: single cells 8 Platelets changing shape during clotting Shape and movement: role of cytoskeleton resting clotting G-actin unpolymerized From Molecular Biology of the Cell/ Lodish F-actin polymerized

5 9 Actin polymerization during cell movement 10 Zone of actin polymerization Front/ leading edge nucleus Direction of movement Lamellipodia/filopodia From Molecular Cell Biology/ Lodish Rear/ trailing edge Rearrangement of microfilaments (F-actin) with cell movement 11 See Purves 4.26 Receptors connect ECM and cytoskeleton 12 Front (leading edge) increased adhesion Cell adhesion and signaling Rear (trailing edge) adhesion loss Adhesion receptors: integrins ECM proteins: collagen, laminin, fibronectin cells cytoskeleton receptors ECM proteins proteoglycans F-actin receptor ligand focal adhesion movement nuc ECM ligand (laminin) binds receptor (integrin) which activates Focal Adhesion Kinase activates GTPase (rac/cdc42/rho) activates profilin which increases F-actin

6 columnar apical 13 cuboidal squamous wedged basal Epithelial sheets and building tubes Cell shape changes via cytoskeleton Flat epithelial sheet Bent epithelial sheet 14 Epithelial sheets can roll or bend to form a tube Examples: brain, spinal cord 15 Ray Keller Amphibian neural tube forms by rolling up an epithelial sheet

7 16 Mesenchymal cells can condense to form a tube Examples: blood vessels, some kidney tubules 17 Purves 48.12: Lung tubules An epithelial sheet can extend to form a tube Example: primary tracheal tubules Lung tubule branching: initial steps

8 20 Single cells can roll or hollow into tubes Examples: secondary and terminal tracheal tubules 21 FGF inhibitor = sprouty FGF (ligand)= branchless FGF receptor = breathless epithelium Primary tubule Secondary Terminal O2 stress genes Primary tracheal outgrowth and branching (Drosophila) See Purves FGF = ligand Receptor (tyrosine kinase) Tubule morphogenesis in culture Purves: 15.9: Fibroblast Growth Factor signaling