formation iii morphogenesis: building 3d structures 7.013 4.6.07
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Formation IIIMorphogenesis: building
3D structures
7.0134.6.07
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STARTSTARTFOUNDATIOFOUNDATIONSNS
How-to 1How-to 1 FO
RM
ATIO
FO
RM
ATIO
NN
How-to 2How-to 2
SYSTEMSYSTEMSSP
RO
BLEM
SP
RO
BLEM
S
BIOCHEM GENETICS CELL BIO.MOL. BIO
STEM CELLS,
CLONING
REC. DNA
POSITION&FATE
3DSTRUCTURE
STEPS
VIRUSES
CANCER
HUMANDISEASE
LIFELIFE
NERVOUSIMMUNE
SYSTEMSBIOLOGY
FUTUREFUTURE
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Dorsal determinationSee Purves 20.3
Egg-catenin - phosphorylated- unstable, cytoplasmic
DV
DV
2-4 cells and older:- determinants inhibit -catenin phosph.- dorsally stable, nuclear
20H. Sive MIT 2007
determinant
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Mesoderm determination
HI
LO
Nodal (ligand) gradient
animal pole
vegetal pole
2 - 500+ cells
mesoderm
Low Nodal induces mesoderm
500+ cells
(High Nodal induces endoderm)
22H. Sive MIT 2007
Nodal binds receptor thatactivates Smad2 txn factor
Nodal ligand
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+DV
-cateninDorsal
500+ cells
low Nodal
Mesoderm
500+ cells
animal pole
vegetal pole
23H. Sive MIT 2007
dorsal mesoderm:-cat + low Nodal(Smad2)activates MyoDtranscription
=Dorsal mesoderm = future muscle
4,000+ cell stage
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Somites: Segments that will form muscle, skeleton and skin
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Biological 3D structures
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Specialized cell shape:neuron
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Organ: kidney
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Lab Grows Bladders From Cells of PatientsWashington PostTuesday, April 4, 2006
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Stages in Xenopus development
egg (0hpf) early blastula (4hpf)
late blastula (8hpf)
neurula (16hpf) tadpole (40h)differentiation
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gastrula (11hpf)movement
division, determination
4H. Sive MIT 2007
first structures
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Pile of cells (blastula)
3D structure(organ)
What processes would turn the pile of cells into a 3D structure? (about 6)
5
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Cell sorting due to differential and homotypic cell adhesion (N-Cadherin vs E-cadherin)
6
Epidermal cellsEpidermal cellsEpidermal cells
Epidermal cells
Neural plate cells
Cell dissociation
Reaggregation
Cell typesorting
Epidermal cellsOutsideNeural inside
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Epithelium:cell sheet
extracellularmatrix (ECM)
apical
basal
Mesenchyme: single cells
Epithelium/mesenchyme and transition
junctions
H. Sive MIT 2007
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Shape and movement:role of cytoskeleton
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G-actinunpolymerized F-actin
polymerized
Platelets changing shape during clotting
resting clotting
From Molecular Biology of the Cell/ Lodish
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From Molecular Cell Biology/ Lodish
Zone of actin polymerization
Front/leading edge
Direction ofmovement
nucleus
Rear/trailingedgeLamellipodia/filopodia
Actin polymerization during cell movement
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Rearrangement of microfilaments (F-actin) with cell movement
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cells
Receptors connect ECM and cytoskeleton
See Purves 4.26
receptors
cytoskeleton
ECM proteinsproteoglycans
Adhesion receptors: integrinsECM proteins: collagen, laminin, fibronectin
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H. Sive MIT 2007
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Front (leading edge)increased adhesion
Rear (trailing edge)adhesion loss
F-actin
ECMreceptor
ligand
focal adhesion
nuc
movement
Cell adhesion and signaling12
H. Sive MIT 2007
ligand (laminin) binds receptor (integrin) which activates Focal Adhesion Kinaseactivates GTPase (rac/cdc42/rho)activates profilin which increases F-actin
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Epithelial sheets andbuilding tubes
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Cell shape changesvia cytoskeleton
cuboidalcolumnar
wedged
Flat epithelial sheet
Bent epithelial sheet
squamous
13 apical
basal
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Epithelial sheets can roll or bend to form a tubeExamples: brain, spinal cord
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Amphibian neural tube forms by rolling up an epithelial sheet
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15 Ray Keller
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Mesenchymal cells can condense to form a tubeExamples: blood vessels, some kidney tubules
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Purves 48.12:Lung tubules
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Lung tubule branching: initial steps
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An epithelial sheet can extend to form a tubeExample: primary tracheal tubules
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Single cells can roll or hollow into tubesExamples: secondary and terminal tracheal tubules
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epithelium
FGF (ligand)= branchlessFGF inhibitor = sprouty
genes
Primary tracheal outgrowth and branching (Drosophila)See Purves 48.5
FGF receptor = breathless
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O2 stress
Primary tubule Secondary Terminal
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Tubule morphogenesis in culture
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15.11
FGF = ligand
Receptor (tyrosine kinase)
Purves: 15.9: Fibroblast Growth Factor signaling
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