How has the study of the origins and development of the neural crest shed light on our understanding of development mechanisms and the origins of development disease?

Define neural crest as the ectodermal cells from the lateral neural plate. They go on to form various parts of the body such as:
Skull + teeth, PNS, calcitonin producing cells, parathyroid glands, carotid bodies, spiral septum, adrenal chromaffin cells.
They start from the neural tube but during development they migrate. Subsequently the study of these have given greater insight into cell migration mechanisms. Furthermore these neural crest cells are plastic and have allowed for improved understanding into how regulative development occurs.
Finally labelling experiments have allowed us to trace the lineage of differentiated cells to form fate maps. This has enabled us to understand the origins of many types of cells are actually neural crest and subsequenty help us to understand why conditions such as DiGeorge’s which causes craniofacial deformities can also cause      thyroid gland agenesis and persistent truncus arteriosus.

Neural crest fate mapping
Much of the knowledge on this was learnt from the early experiments of Nicole Le Douarin. She did experiments where she grafted the neural crest cells of a quail onto a chicken. (this allowed for identification due to differing heterochromatin patterns after staining). She then examined the fate of cells for different parts of the neural crest.
It showed that different parts of the neural crest adopted different fates:
Cranial - invade pharyngeal arches and around the brain. To form neurons, glia of sensory and parasympathetic cranial ganglia, dermis, menignes, teeth, bulk of the skull, melanocytes, thymus, parathyroids.

Vagal neural crest cells from the caudal hindbrain invade the gut and heart forming the ENS and aortico-pulmonary septum.

Trunk neural crest cells include all the neurons and glia of the sensory and sympathetic ganglia, adrenal medullary chromaffin cells, schwann cells and melanocytes.

Multipotency + regulative development
Subsequent to Nicole Le Douarin’s experiment, labelling of single cells were possible and this showed that even from the same region of neural crest, a single cell can form 2 different fates. For example a trunk vagal cell may form both the adrenal medullary chrommafin cells and also melanocytes. This showed that the neural crests were under regulative control
Furthermore in vitro and vivo experiments showed that a single neural crest cell can adopt different fates depending on its morphogen environment:
BMP4 which would be around the dorsal aorta causes sympathetic neuron fate
Neuregulin 1 type 3 instructs schwann cell fate
FGF2 instructs cartilage fate.
Furthermore transplant of trunk neural crest cells into vagal positions will result in the formation of a vagal phenotype.
Migration
Neural crest migration experiments helped elucidate a lot of info about migration.  It was found that ECM proteins such as fibronectin, laminin, tenascin and collagen all promoted migration and it was dependent on the NC cells having the corresponding integrins for them.
However to guide the cells there are repulsive factors such as sema3 and ephrinb which repel NC cells which express neuropillin and eph receptors. This was shown in Rodger Keynes experiment in which he proved that the reason why NC cells migrated through the caudal side of the somite was due to repulsive cues from the somite (shown as he surgically rotated the somites which resulted in the NC cells coming through the rostral side. To differentiate whether there were attractive or repulsive signals was shown with K.O experiments.
Long range attractive cues are also used and this is seen in the formation of the ENS whereby ret is expressed by the vagal neural crest cells that will form the enteric ganglia. They are attracted by GDNF from the gut cells. Mutation of c-Ret results in hirschprung’s disease.
Another area where migration and signalling patterns have been studied is in the pharyngeal pounces where the cranial neural crest cells migrate in distinct streams.
Consider the following barriers:
a1 there is an r3 level inhibitory signal (which in mice,chick and zfish is sema3).
ba2 at the r5 level is a physical barrier of the otic vesicle.
ba3 is another inhibitory signal which segregates the 3+4th arch in frogs and is Ephrin/Eph signalling.

We particularly see the importance of the physical barrier of the otic vesicle.
Diseases
The combination of the research of all the above mechanisms have allowed for the increase our knowledge on NC diseases.
As mentioned earlier hirschprung’s disease can occur due to c-ret mutation or mutation in the signalling moleucles such as BMP4 or neuregulin.
However the most common set of diseases are craniofacial malformations.
Cleft lip and cleft palate are failures of maxillary swellings to fuse but any of the 5 neural crest bulges can fail to fuse resulting in abnormal development.

This is linked with deletion of chromosome 22q11 which removes the Tbx1 gene. And causes Digeorge and Velocardiofacial syndrome, suggesting tbx1 is involved in craniofacial migration.
Originally written by Hilary Kosterlitz

Popular posts from this blog

The inspector calls and how it relates to biblical parables.

The Parable of the Sower, The Good Samaritan, The Prodigal Son The Parable Of The Sower There was a farmer who went to sow some corn. He scattered the seeds in the field and the seeds fell in various places. Some of the seed fell on the path where it was eaten by birds and stepped on. Some of the seed fell on rocky ground, and the plants sprouted but dried up because the soil had no moisture. Some of the seed fell in a thorn bush and grew up but were choked by the thorns. Lastly some seed fell on good soil and the plants grew and produced lots of grains. Jesus then explains the parable and says: The seeds that fell on the path represent those who hear, but the devil comes and takes the message from the hearts and stops them from being saved. The seeds that fell on the rocky ground represent the people who except gods message gladly but it doesn’t sink in and when there faith is on the line they fade away The seeds that fall among thorn...
Read more

How does Priestley convey his message in An Inspector Calls?

Being a co-founder of the Socialist Commonwealth Party, Priestley felt that his political views on socialism were very important and these views are displayed prominently throughout An Inspector Calls. Priestley uses characters to represent the different generations and also uses the Inspector as a mouthpiece to distribute his views; several critics describe the Inspector as Priestley’s alter ego. The Inspector conveys Priestley’s most important message, that a change in society’s attitude is required. Through Sheila’s words, “of course he knows. And I hate to think how much he knows that we don’t already know yet” we can see that the Inspector is believed to be an omniscient presence. He speaks as if he is divine by referring to the people as men and during his last speech he says, “If men will not learn that lesson, they will be taught it in fire and blood and anguish.” These words are influenced by Priestley’s own experiences fighting in the First World War. Portraying the Inspec...
Read more

Tybalt is to blame for this tragedy - Romeo and Juliet Essay

“Tybalt is to blame for this tragedy” discuss with reference to Act 3 Scene 1 On one hand, Tybalt is heavily involved in the build up to the tragedy in Romeo and Juliet; Shakespeare portrays him as a villainous character who is the cause of several deaths and misfortune. Throughout the play Shakespeare exposes Tybalt’s violent nature and his anger is particularly shown, when Tybalt confronts Romeo and insults him in Act 3 Scene 1 saying, ‘thou art a villain’. This, in the Elizabethan period was very insulting and shows how quick Tybalt is to start fights, proving that he is hot-tempered. Critics argue that Tybalt caused the tragedy as he encourages a brawl by inviting Romeo to ‘turn and draw’. Had Tybalt not said this, Mercutio would probably not have been provoked to fight and consequently die. As a result of Mercutio’s death, Romeo killed Tybalt, forcing Romeo to leave. This led to a chain of disastrous events resulting in Romeo’s, Juliet’s and Paris’ deaths. It can also be argu...
Read more

Why George R.R. Martin Reigns Supreme Over J.R.R. Tolkien

When it comes to the world of epic fantasy literature, two names stand out: George R.R. Martin and J.R.R. Tolkien. Both authors have captivated readers with their immersive worlds and richly crafted characters, but when it comes to comparing the two, George R.R. Martin undeniably takes the throne as the superior storyteller. One of the reasons why Martin surpasses Tolkien is his realistic and complex portrayal of human nature. Martin's characters are flawed, multi-dimensional, and morally ambiguous, making them relatable and compelling. He doesn't shy away from depicting the darker aspects of human behavior, such as political intrigue, betrayal, and the consequences of power struggles. In contrast, Tolkien's characters tend to be more archetypal, with clear-cut divisions between good and evil, and less depth in their motivations and actions. Furthermore, Martin's world-building is unparalleled in its intricacy and detail. The fictional realm of Westeros in his "A S...
Read more

The Mayor of Casterbridge - Why is the ring at Casterbridge a suitable place for Henchard to meet Susan?

Why is the ring at Casterbridge a suitable place for Henchard to meet Susan? There are a number of reasons why the Ring could be considered a suitable place for Henchard to meet Susan. Firstly, Hardy makes it clear the Ring is not a place of happiness. It is described as a Roman amphitheatre in the heart of Casterbridge where no joy can be found, even for boys who tried to play cricket in it. He even accounts the story of a woman who murdered her husband being put at the stake in the Ring. This could suggest the Ring was a suitable place for the meeting as just as an evil woman was put to rest in the Ring, so will Henchard’s terrible and disgraceful mistake. As the Mayor of Casterbridge, Henchard is considered as a very respectable man and it would greatly damage his reputation if people discovered he had sold his wife and child. This is another reason the Ring was such a suitable place for the couple to meet as it is the “spot as being safest from observation which he cou...
Read more

What is the most influential passage in the Bible?

  The Bible is one of the most widely-read and influential books in human history. It is the primary religious text for Christians and is considered a source of guidance, wisdom, and spiritual insight. Throughout the Bible, there are many passages that have had a profound impact on the world and have shaped the course of human history. One of the most influential Bible passages is the Sermon on the Mount, found in the Gospel of Matthew. The Sermon on the Mount is a collection of teachings and sayings of Jesus, delivered on a mountainside to a large crowd of followers. The sermon is recorded in Matthew 5-7 and covers a wide range of topics, including morality, ethics, prayer, and faith. It includes some of the most famous teachings of Jesus, such as the Beatitudes, the Lord's Prayer, and the Golden Rule. The Beatitudes, found in Matthew 5:3-12, are a series of blessings that describe the characteristics and virtues of a blessed life. These blessings have been interpreted in differen...
Read more