Formation IIIMorphogenesis: building

3D structures

7.0134.6.07

STARTSTART

FOUNDATIOFOUNDATIONSNS

How-to 1How-to 1 FORM

ATIO

FORM

ATIO

NN

How-to 2How-to 2

SYSTEMSYSTEMSSPR

OBL

EMS

PRO

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+ cellsanimal 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

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Biological 3D structures

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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

4 H. 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

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Cell sorting due to differential and homotypic cell adhesion (N-Cadherin vs E-cadherin)

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Epidermal cellsEpidermal cellsEpidermal cellsEpidermal cells

Neural plate cells

Cell dissociation

ReaggregationCell 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

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cells

Receptors connect ECM and cytoskeletonSee 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

ECMreceptorligand

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

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Amphibian neural tube forms by rolling up an epithelial sheet

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15 Ray Keller

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

21

O2 stress

Primary tubule Secondary Terminal

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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