Development of the Vascular System

Question 1

Endothelial cells are derived from . . .

Answer 1

the mesoderm

Question 2

pericytes

Answer 2

Mural cells of capilaries

Smooth muscle-like cell that sits outside of a capilary and stabilizes the tissue.

Question 3

Vasculogenesis

Answer 3

The way blood vessels are initially formed de novo

Only occurs in the yolk sack and dorsal aorta/cardinal vein during embryogenesis

Question 4

Angiogenesis

Answer 4

The process by which existing vascular networks are extended or modified

Question 5

In mammals, the yolk sack circulation has evolved to become. . .

Answer 5

the umbilical circulation

Question 6

Hemangioblast

Answer 6

Common progenitor of hematopoietic stem cells and endothelial cells.

Question 7

Blood islands

Answer 7

Clusters of hemangioblasts that form during development of the yolk sack.

Quickly link up to form a developing capillary network, with hematopoietic stem cells in the middle and angioblasts surrounding.

Question 8

Sites of hematopoiesis

Answer 8

1. Yolk sack
2. Fetal liver
3. Bone marrow

Question 9

Sprouting and remodeling in angiogenesis

Answer 9

Tip cells extend via highly motile and dynamic filopodia driven by growth cones similar to those seen in axon tips.

Question 10

Quiescent vessel

Answer 10

Not actively growing or changing

Question 11

Partial EMT

Answer 11

Seen in tip cells that are induced by VEGF from quiescent vessels.

Cell grows filopodia and changes gene expression profile, but does not detatch from its epithelial neighbors.

Note that tip cells are not proliferative, but stalk cells are.

Question 12

Rough mechanism of blood vessel branching

Answer 12

Note that there is only one tip cell and it does not proliferate. Only the stalk cells proliferate.

Question 13

Recruitment of mural cells

Answer 13

Mediated by platelet-derived growth factor that is in turn produced by endothelial cells.

Causes differentiation of mesenchymal cells into mural cells. Also promotes mural cell proliferation, survival, and differentiation.

Question 14

Angiopoietin-1

Answer 14

Produced by mural cells and acts on endothelial cells. Promotes endothelial cell survival and stable interaction between endothelial cells.

Question 15

Epithelial-mesenchymal interactions

Answer 15

Widespread in development

Communication via growth factors between epithelial cells and supporting mesenchymal cells that enables coordinated development and tissue maintenance.

Ex. Endothelial cells produce PDGF to stimulate mural cell survival, mural cells produce angiopoietin-1 to stimulate endothelial cell survival.

Question 16

Vein endothelial cells express ___. Artery endothelial cells express ___.

Answer 16

Vein endothelial cells express Eph. Artery endothelial cells express ephrin.

Question 17

Axon growth cone vs endothelial tip cell

Answer 17

Question 18

Intersomitic vessels

Answer 18

Blood vessels that form between somites during development.

Give rise to the intercostal vaculation, among other structures.

Question 19

During segmental stages of development, extending nerve axons and vacular networks. . .

Answer 19

share the same guidance ques.

Even expressing the same receptor!

Question 20

In the skin, ___ lead the way and ___ follow.

Answer 20

In the skin, axons lead the way and vascular tissues follow.

This is mediated by nerve VEGF production, which guides the vascular tissue to follow and vasculate it.

Question 21

How do we ensure that blood vessels go where they need to go?

Answer 21

Hypoxia!!!

VEGF production is induced by HIF1α

Question 22

The problem with hypoxia-driven vasculation during development

Answer 22

Some tissues (namely skeletal muscle) have little need for vasculation during development, but need to be well vasculated postnatally.

Solution: VEGF is upregulated as part of the muscle differentiation and development program (ie it is under a MyoD-regulated enhancer), ensuring adequate VEGF production despite oxygenation state.

Question 23

Rough outline of Notch signaling

Answer 23

Question 24

γ-secretase

Answer 24

Intracellular membrane-bound enzyme which cleaves the Notch intracellular domain to generate an NCID transcription factor as part of Notch signaling.

Question 25

Dibenzazepine

Answer 25

γ-secretase inhibitor