Development of the Vascular System Flashcards
Endothelial cells are derived from . . .
the mesoderm
pericytes
Mural cells of capilaries
Smooth muscle-like cell that sits outside of a capilary and stabilizes the tissue.
Vasculogenesis
The way blood vessels are initially formed de novo
Only occurs in the yolk sack and dorsal aorta/cardinal vein during embryogenesis
Angiogenesis
The process by which existing vascular networks are extended or modified
In mammals, the yolk sack circulation has evolved to become. . .
the umbilical circulation
Hemangioblast
Common progenitor of hematopoietic stem cells and endothelial cells.
Blood islands
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.
Sites of hematopoiesis
- Yolk sack
- Fetal liver
- Bone marrow
Sprouting and remodeling in angiogenesis
Tip cells extend via highly motile and dynamic filopodia driven by growth cones similar to those seen in axon tips.
Quiescent vessel
Not actively growing or changing
Partial EMT
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.
Rough mechanism of blood vessel branching
Note that there is only one tip cell and it does not proliferate. Only the stalk cells proliferate.
Recruitment of mural cells
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.
Angiopoietin-1
Produced by mural cells and acts on endothelial cells. Promotes endothelial cell survival and stable interaction between endothelial cells.
Epithelial-mesenchymal interactions
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.
Vein endothelial cells express ___. Artery endothelial cells express ___.
Vein endothelial cells express Eph. Artery endothelial cells express ephrin.
Axon growth cone vs endothelial tip cell
Intersomitic vessels
Blood vessels that form between somites during development.
Give rise to the intercostal vaculation, among other structures.
During segmental stages of development, extending nerve axons and vacular networks. . .
share the same guidance ques.
Even expressing the same receptor!
In the skin, ___ lead the way and ___ follow.
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.
How do we ensure that blood vessels go where they need to go?
Hypoxia!!!
VEGF production is induced by HIF1α
The problem with hypoxia-driven vasculation during development
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.
Rough outline of Notch signaling
γ-secretase
Intracellular membrane-bound enzyme which cleaves the Notch intracellular domain to generate an NCID transcription factor as part of Notch signaling.
