L16-17: Vasculature Development

Question 1

Are signalling pathways in veins and arteries different?

Answer 1

No.

Question 2

What does ephrin B2 signalling do?

Answer 2

• promote directional cell migration and invasion

- suppress cell apoptosis

Question 3

What is angiogenesis and vasculogenesis?

Answer 3

Vasculogenesis is formation of new blood vessels

Angiogenesis is branching from existing vessels to create new ones

Question 4

Cell transitions in becoming blood vessels

Answer 4

mesoderm > hemangioblasts > angioblasts > endothelial cells

Question 5

Where is extraemryonic vasculogenesis taking place?

Answer 5

in the yolk sac

Question 6

Where is intraembryogenic vasculogenesis taking place?

Answer 6

dorsal aorta and vessels between organs

Question 7

What are the steps in vasculogenesis?

Answer 7

1. condensation
2. Differentiation
3. epithelialization

Question 8

What inhibits the proliferation of endothelial cells?

Answer 8

contact with the capillary basement membrane

Question 9

What are some markers of quiescent endothelial cells?

Answer 9

PECAM, L-selectin

Question 10

What are some markers of angiogenic endothelial cells?

Answer 10

TFG-β receptor

Question 11

What are the three types of endothelial cells? Where are they found

Answer 11

continuous. muscle, brain, heart

fenestrated, discontinuous. endo/exocrine organs. for easier transport

Question 12

what the big difference between discontinous and continous/fenestrated endo cells

Answer 12

No basal membrane on discontinuous

Question 13

What are some support cells that wrap around the endothelial cells?

Answer 13

pericytes and other mural cells

Question 14

What connects mural cells to endo cells?

Answer 14

angiopoetins on mural cells and Tie2 receptors on endo cells

Question 15

What type of cell give rise to endo and mural cells?

Answer 15

vascular progenitor

Question 16

Which VEGFR can exist in free soluble but inactive form?

Answer 16

VEGFR1

Question 17

Which receptors can bind VEGFA?

Answer 17

VEGFR 1 and 2

Question 18

Which VEGFR is not necessary in angiogenesis?

Answer 18

VEGFR 3

Question 19

What would happen without mural cells?

Answer 19

severe edema. makes sense because there would vasodialation without control?

Question 20

What is interesting about VEGFR1 role in vasculogenesis?

Answer 20

Even without the kinase domain, it had no negative effect on vasculogenesis. But total removal results in lower vasculogenesis.

Question 21

What is the primary role of VEGFR1?

Answer 21

Recruit macrophages to release

Question 22

What is essential for vasculogensis and what is not?

Answer 22

VEGFR2 and VEGFA is.

VEGFR1 is not

Question 23

What are three functions of VEGFR2?

Answer 23

proliferation, survival and motility

Question 24

Describe how boyden chamber assay works

Answer 24

Plate cells. Put chemoattractants and see the migration of the cells above or below the plate

Question 25

VEGF in angiogenesis. What does it do?

Answer 25

- FAK pathway > stress fibre and focal adhesion > cell migration towards VEGF source - cell proliferation - tube formation

Question 26

What part leads to the formation of vascular tube?

Answer 26

intracellular vacuoles

Question 27

Difference between VEGF and bFGF?

Answer 27

VEGF is specific for endo cells. bFGF is not.

Question 28

What is non sprouting angiogenesis and how does it happen?

Answer 28

fibroblasts wrap around the vessels to form pillars and split in half.

Question 29

What kind of remodelling can be done during angiogenesis? How?

Answer 29

splitting and removal of vessels. Through pillar formation

Question 30

What process ensures that only one cell becomes tip cell?

Answer 30

lateral inhibition

Question 31

Explain lateral inhibition

Answer 31

Single cell with many delta binds to multiple cells with notch. This inhibits all cells with notch. So only one cell produces VEGFR2 and migrates

Question 32

How are veins and arteries merged together?

Answer 32

EphB4 on veins and Epherin B2 on arteries. Reverse signalling.

Question 33

Describe reverse signalling on eph pathway

Answer 33

On the ligand side, the signalling downstream happens.

Question 34

What happens in forward and reverse signalling in eph pathway for angiogenesis.

Answer 34

forward. Repulsion | Backward. cell migration

Question 35

Which direction of eph signalling defines the boundaries between arteries and veins?

Answer 35

forward

Question 36

How do tumors abuse eph signalling?

Answer 36

overproduce ephB4 to form more arteries towards it.

Question 37

How far is every cell from a capillary?

Answer 37

50-100μm

Question 38

Does angiogenesis happen during injury?

Answer 38

ya. duh

Question 39

What happens in hypoxia? Details

Answer 39

hypoxia > HIF1α is not degraded > binds with β > becomes a transcriptional factor > VEGF

Question 40

How is angiogenesis basal membrane breakdown possible?

Answer 40

MMP

Question 41

What are two types of MMP and what they break down

Answer 41

MMP2(gelatinase A) - collagen I, IV, V, fibrillar collagen MMP9(gelatinase B) - collagen IV, V

Question 42

Are MMPs pro or anti angiogenic?

Answer 42

both

Question 43

How does VEGF increase permiability?

Answer 43

VEGF > Fak > bind to cadherine > βcatening released > no adherens junction

Question 44

Explain how MMPs are anti angiogenic

Answer 44

- can increase competition for MMP2 | - cleave ligand binding domain of VEGFR1

Question 45

Explain how MMPs are pro angiogenic

Answer 45

- basal membrane disintegration - MMP2 bind to integrins - release more VEGF - cleavage of VE-cadherins - release bFGF and activate TGFβ