MC - Vascular & Nervous System Development Flashcards
What is generally believed to first, nervous or vascular systems?
Generally believed that modern nervous systems arose first in the form of diffuse nerve-nets, in sea-dwelling organisms (such as cnidarians).
- The first nervous systems lacked blood, so it is postulated that the nervous systems preceded the vascular system.
What was the major driving force behind vascular evolution?
The need for oxygen to fuel aerobic metabolism in multicellular organisms, combined with the limited ability of oxygen to diffuse through tissue (especially to deep tissue structures).
What is neurofilament?
A marker used to label neurons.
What is FLK1?
A marker used to label blood vessels.
What is FD40?
A marker used to fluorescently label blood vessels (inside the lumen).
What is involved in vascular remodelling?
A robust vascular plexus is generated in the embryo, followed by remodelling to arteries, veins, and fine capillary networks.
When does vascular remodelling take place?
After peripheral nerve development, and is directed by peripheral sensory neurons and Schwann cells.
Who is considered to be the father of modern neuroscience?
Santiago Ramón y Cajal.
What was Cajal’s say on the developing neuron?
That it was “like a battering-ram, soft and flexible, which advances mechanically, pushing aside the obstacles that it finds in its way until it reaches its peripheral destination.”
What is the growth cone?
A highly motile structure that explores the extracellular environment, determining the direction of growth of the neuron, and then guiding the extension of the axon in that direction.
- Dynamic in nature
- Responds (biochemically) to the surrounding environment by rapidly changing direction and branching in response to various stimuli (growth factors)
What is observed regarding endothelial cells and neural stem cells during development?
Endothelial cells and neural stems cells are found in similar locations and developmental stages in the neural germinal zones.
What are axon guidance molecules?
Generally soluble proteins which guide the axon growth.
- Produced by developing neurons and developing endothelial cells
Give some examples of major axon guidance molecules.
- Semaphorins
- Ephrin
- Netrin
- Slit
What are semaphorins?
Membrane-associated proteins that are involved in axon repulsion and/or attraction.
What is VEGF?
Vascular endothelial growth factor (VEGF) is a potent molecule that allows blood vessels to develop.
- Essential to have sufficient levels of VEGF in the embryonic animal/human brain during development
- Also essential that it is regulated properly (i.e., turned ON and OFF at specific timepoints)
What happens if VEGF levels are too high (e.g., in the brain or the eye)?
Can cause a whole range of problems as they can start to tell well-developed/adult vasculature to go back to their developmental stage (i.e., start proliferating again), which is NOT what we want.
- Thus, VEGF has become a really hot therapeutic target for many diseases
- With many diseases responding to anti-VEGF therapy
- E.g., Diabetic retinopathy, where blood vessels in the inner retina begin to proliferate due to high levels of VEGF
What are vascular guidance molecules?
Molecular cues that guide vascular growth.
Give some examples of vascular guidance molecules.
- VEGF
- Slit 1-3
What is considered as the master regulator of vascular development?
VEGF.
- VEGF is being switched on at the critical timepoints in development when decisions need to be made by neurons and endothelial cells (in terms of direction and speed of growth)
How does VEGF respond to certain stress?
If exposed to hypoxia, VEGF is switched back on to control vasculogenesis and angiogenesis (i.e., it is a hypoxia-sensitive gene).
- Has disease implications (i.e., VEGF can be regulated to treat disease)
What is a xenograft?
A tissue or organ that is derived from a species being transplanted into a recipient species of a different lineage.
What is different about brain endothelial cells compared to peripheral endothelial cells?
Brain endothelial cells express specific genes that are not expressed in peripheral endothelial cells.
Give an example of a famous experiment that looked at brain endothelial cells compared to peripheral endothelial cells.
Chick-quail xenografts in which vessels of the coelimic cavity of the embryonic chick acquired BBB characteristics when transplanted into the quail brain (i.e., peripheral endothelial cells began to look like brain endothelial cells).
This suggests that the brain endothelial cells are getting their properties from the surrounding soluble microenvironment (i.e., they are NOT unique transcriptionally).
What is the blood brain barrier (BBB)?
Used to describe the unique properties of the microvasculature of the central nervous system (CNS).
- In other words, it describes the cells that line blood vessels in the brain (i.e., brain endothelial cells)
- Highly selective (on what they let in and out)
