Formation III

Morphogenesis:

building 3D structures

7.013

4.6.07

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SYSTEMSSYSTEMS

PR

OB

LE

MS

PR

OB

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BIOCHEM GENETICS CELL BIO.MOL. BIO

STEM

CELLS,

CLONING

REC. DNA

POSITION&FATE

3DSTRUCTURE

STEPS

VIRUSES

CANCER

HUMAN

DISEASE

LIFELIFE

NERVOUSIMMUNE

SYSTEMS

BIOLOGY

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 that

activates 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 MyoD

transcription

=Dorsal mesoderm = future muscle

4,000+ cell stage

Somites:

Segments that will form muscle, skeleton and skin

Biological 3D structuresSpecialized cell shape:

neuron

1

Organ: kidney

2 Lab Grows Bladders From Cells of Patients

Washington Post

Tuesday, April 4, 2006

3

Stages in Xenopus development

egg (0hpf) early blastula

(4hpf)

late blastula

(8hpf)

neurula (16hpf) tadpole (40h)

differentiation

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

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 type

sorting

Epidermal cells

Outside

Neural inside

Epithelium:

cell sheet

extracellular

matrix (ECM)

apical

basal

Mesenchyme:

single cells

Epithelium/mesenchyme and transition

junctions

H. Sive MIT 2007

7

Shape and movement:

role of cytoskeleton

G-actin

unpolymerized 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 of

movement

nucleus

Rear/

trailing

edgeLamellipodia/filopodia

Actin polymerization during cell movement

Rearrangement of microfilaments (F-actin)

with cell movement

10

cells

Receptors connect ECM and cytoskeleton

See Purves 4.26

receptors

cytoskeleton

ECM

proteins

proteoglycans

Adhesion receptors: integrins

ECM 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 Kinase

activates GTPase (rac/cdc42/rho)

activates profilin which increases F-actin

Epithelial sheets and

building tubes

Cell shape changes

via cytoskeleton

cuboidalcolumnar

wedged

Flat epithelial sheet

Bent epithelial sheet

squamous

13 apical

basal

Epithelial sheets can roll or bend to form a tube

Examples: brain, spinal cord

14

Amphibian neural tube forms by

rolling up an epithelial sheet

15 Ray Keller

Mesenchymal cells can condense to form a tube

Examples: 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 tube

Example: primary tracheal tubules

19

Single cells can roll or hollow into tubes

Examples: secondary and terminal tracheal tubules

20

epithelium

FGF (ligand)= branchless

FGF 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

22

15.11

FGF = ligand

Receptor (tyrosine kinase)

Purves: 15.9: Fibroblast Growth Factor signaling

23