Formation IIIMorphogenesis: building

3D structures

7.0134.6.07

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

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

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

+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

Somites: Segments that will form muscle, skeleton and skin

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Biological 3D structures

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

Specialized cell shape:neuron

1

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

Organ: kidney

2

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Lab Grows Bladders From Cells of PatientsWashington PostTuesday, April 4, 2006

3

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Stages in Xenopus development

egg (0hpf) early blastula (4hpf)

late blastula (8hpf)

neurula (16hpf) tadpole (40h)differentiation

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

gastrula (11hpf)movement

division, determination

4H. Sive MIT 2007

first structures

Pile of cells (blastula)

3D structure(organ)

What processes would turn the pile of cells into a 3D structure? (about 6)

5

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

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

Epithelium:cell sheet

extracellularmatrix (ECM)

apical

basal

Mesenchyme: single cells

Epithelium/mesenchyme and transition

junctions

H. Sive MIT 2007

7

Shape and movement:role of cytoskeleton

G-actinunpolymerized F-actin

polymerized

Platelets changing shape during clotting

resting clotting

From Molecular Biology of the Cell/ Lodish

8

9

From Molecular Cell Biology/ Lodish

Zone of actin polymerization

Front/leading edge

Direction ofmovement

nucleus

Rear/trailingedgeLamellipodia/filopodia

Actin polymerization during cell movement

Rearrangement of microfilaments (F-actin) with cell movement

QuickTime™ and aPhoto decompressor

are needed to see this picture.

10

cells

Receptors connect ECM and cytoskeleton

See Purves 4.26

receptors

cytoskeleton

ECM proteinsproteoglycans

Adhesion receptors: integrinsECM proteins: collagen, laminin, fibronectin

11

H. Sive MIT 2007

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

Epithelial sheets andbuilding tubes

Cell shape changesvia cytoskeleton

cuboidalcolumnar

wedged

Flat epithelial sheet

Bent epithelial sheet

squamous

13 apical

basal

Epithelial sheets can roll or bend to form a tubeExamples: brain, spinal cord

14

Amphibian neural tube forms by rolling up an epithelial sheet

QuickTime™ and aMotion JPEG B decompressor

are needed to see this picture.

15 Ray Keller

Mesenchymal cells can condense to form a tubeExamples: blood vessels, some kidney tubules

16

Purves 48.12:Lung tubules

17

Lung tubule branching: initial steps

18

An epithelial sheet can extend to form a tubeExample: primary tracheal tubules

19

Single cells can roll or hollow into tubesExamples: secondary and terminal tracheal tubules

20

epithelium

FGF (ligand)= branchlessFGF inhibitor = sprouty

genes

Primary tracheal outgrowth and branching (Drosophila)See Purves 48.5

FGF receptor = breathless

21

O2 stress

Primary tubule Secondary Terminal

Tubule morphogenesis in culture

QuickTime™ and aVideo decompressor

are needed to see this picture.

22

15.11

FGF = ligand

Receptor (tyrosine kinase)

Purves: 15.9: Fibroblast Growth Factor signaling

23