1. Formation III Morphogenesis: building 3D structures
Formation III Morphogenesis: building 3D structures

2. LIFE START FUTURE How-to 2 PROBLEMS FORMATION SYSTEMS How-to 1
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. 20 V D V D Dorsal determination Egg b-catenin phosphorylated
H. Sive MIT 2007 20
Dorsal determination
See Purves 20.3 V D
Egg
b-catenin
phosphorylated
unstable, cytoplasmic V D
2-4 cells and older:
determinants inhibit b-catenin phosph.
dorsally stable, nuclear
determinant

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

5. + = 23 V D animal pole 500+ cells 500+ cells low Nodal b-catenin
H. Sive MIT 2007 23
500+ cells
500+ cells +
low Nodal V D
b-catenin
Mesoderm
Dorsal
dorsal
mesoderm:
b-cat + low Nodal
(Smad2)
activates MyoD
transcription =
Dorsal mesoderm = future muscle
4,000+ cell stage
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. 4 egg (0hpf) early blastula (4hpf) late blastula (8hpf)
H. Sive MIT 2007
egg (0hpf)
early blastula
(4hpf)
late blastula
(8hpf)
division, determination
Stages in Xenopus development
gastrula (11hpf)
movement
neurula (16hpf)
tadpole (40h)
differentiation
first structures

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

13. 6 Epidermal Epidermal Epidermal cells Epidermal cells cells 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. 7 Epithelium/mesenchyme and transition apical Epithelium: cell sheet
junctions
basal
extracellular
matrix (ECM)
Mesenchyme:
single cells
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
From Molecular Cell Biology/ Lodish
Zone of actin polymerization
Front/
leading edge
Direction of
movement
nucleus
Rear/
trailing
edge
Lamellipodia/filopodia
Actin polymerization during cell movement

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

19. Receptors connect ECM and cytoskeleton11
See Purves 4.26
Receptors connect ECM and cytoskeleton
cells
cytoskeleton
receptors
ECM
proteins
proteoglycans
Adhesion receptors: integrins
ECM proteins: collagen, laminin, fibronectin
H. Sive MIT 2007

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

21. Epithelial sheets and
building tubes

22. 13 apical 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. Amphibian neural tube forms by rolling up an epithelial sheet15
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. Primary tracheal outgrowth and branching (Drosophila)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 48.5

31. 22
Tubule morphogenesis in culture

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