Team Members: Arastu Jahanbin
& Lindsay Dobrovolny
Team Members: Arastu Jahanbin
& Lindsay Dobrovolny
References & reference Images:
|
|
|
|
|
Comments :
In our animations we attempted to show the migration pathways of
neural crest cells. The neural crest is a transitory structure, with
its cells having a major role in ectodermal development. "Neural
crest cells have the property of having to migrate far from their
source of origin to specific places in the embryo (Gilbert 2000)."
"They have to recognize cues to begin this migration and respond to
signals that guide them along specific routes to their final
destination (Gilbert 2000)."
Neural crest cells are derived from the ectoderm and originate at the dorsal most region of the neural tube. Their importance lies in their ability to migrate extensively and generate various differentiated cell types. Neurons, glial cells, the epinephrine-producing cells of the adrenal gland, pigmented cells of the epidermis, and various skeletal and connective tissue of the head are some of the fates that await neural crest cells. These fates are determined to a large degree on where the cells migrate.
Neural crest cells can be grouped into functional types; trunk neural crest, cranial neural crest, and cardiac neural crest. We will follow the various pathways taken by each type of neural crest and examine the factors that promote their differentiation.
For cells to leave the neural crest, RhoB and Slug protein must be present. "RhoB establishes the cytoskeletal conditions that promote migration, while Slug activates factors that dissociate the tight junctions between cells (Gilbert 2000)." The loss of
N-cadherin also helps to initiate the migration of neural crests cells.
Our first animation does an excellent job of showing the two major pathways that trunk neural crest cells travel on. They can either migrate along a dorsolateral or ventral pathway. "Those cells migrating along the dorsolateral pathway travel through the dermis, entering the ectoderm through minute holes in the basal lamina and become melanocytes (Gilbert 2000)." "In the second pathway cells migrate ventrally through the anterior but not through the posterior section of the sclerotomes to eventually become sensory (dorsal root) and sympathetic neurons, adrenomedullary cells, and Schwann cells (Gilbert 2000)."
One area that our first animation could be expanded on in the future is for it to show the roles that various proteins in the surronding extracellular matrix play in promoting and restricting migration. "Proteins such as fibronectin, laminin, tenascin, various collagen molecules, and proteoglycans promote migration; while ephrins proteins mark where neural crest cells do not go (Gilbert 2000)."
Trunk neural crest cells show the ability to be pluripotent, their final differentiation is determined to a large extent by the environment into which they travel, surronding tissues in conjunction with extracellular matrices direct their result.
Our second animation shows cranial neural crest cell migration into the pharyngeal arches, and Hox expression patterns. "The cranial, or cephalic, neural crest has cells that migrate dorsolaterally to produce the craniofacial mesenchyme that differentiates into the cartilage, bone, cranial neurons, glia, and connective tissue of the face (Gilbert 2000)." Cranial neural crest cells unlike the trunk neural crest cells have the capability to produce cartilage and bone. The pathway that these cells take leads them into the pharyngeal arches and pouches where they will give rise to certain structures to be shown later.
Our animation shows that there are three major pathways that cranial neural crest cells anterior to the 6th rhombomere take. Neural crest cells from the 2nd and 4th rhombomeres migrate to the 1st and 2nd pharyngeal arches respectively, while cells from the 6th rhombomere travel into the 3rd and 4th pharyngeal arch. Neural crest cells from the 3rd and 5th rhombomeres do not migrate through the mesoderm but instead enter the migrating streams of an adjacent rhombomere. An important note that our animation does not show is that these streams are kept separated via ephrins. If these ephrins receptors are blocked the different streams will mix together.
The most complex part of the cranial neural crest migration is the understanding of the how the combinations of Hox genes are expressed to specify the fate of the cells. In the rhombomeres Hox gene expression boundaries coincide with the rhombomere borders. There are no Hox genes expressed in the first two rhombomeres thus the neural crest cell has no Hox genes, determining these cells to migrate to pharyngeal arch 1. The neural crest cells that migrate from rhombomere 4 have Hoxb-2 and Hoxb-1 expressed, this determines them to migrate to pharyngeal arch 2. Cells that migrate from the 6th rhombomere have Hoxb-2 as well as Hoxb-3 expressed causing their migration to the 3rd pharyngeal arch. Lastly the cells that end their migration in the 4th arch have Hoxb-2, Hoxb-3 and Hoxb-4 expressed. If these Hox genes are knocked out then there is no migration to the 2nd, 3rd and 4th pharyngeal arch.
Once in the pharyngeal arches and pouches, the neural crest cells have to continue proliferating and then differentiate. The cells in the 1st pharyngeal arch are responsible for the formation of the jawbones as well as the incus and malleus bones of the ear. "They are also pulled by the expanding epidermis to form the frontonasal process (Gilbert 2000)." The frontonasal process is what is responsible for the generation of the bones of the face. "The cells that make their way into the 2nd arch end up forming the hyoid cartilage of the neck (Gilbert 2000)." The thymus, parathyroid, and thyroid glands all are derived from the 3rd and 4th pharyngeal arch. If the neural crest cells are removed from, or are blocked form migrating from rhombomere 6 then these glands will fail to form. The absence or presence of various Hox genes in the arches also has a great impact on whether the neural crest cells will differentiate properly. For instance, "when Hoxa-2 is knocked out from mouse embryos, the neural crest cells of the second pharyngeal arch are transformed into those structures of the first pharyngeal arch (Gilbert 2000)."
A future addition to this animation could be to show the actual proliferation and differentiation of the cranial neural crest cells into the various components of the face. Making an animation of diagram 13.7 C would help to show what happens to the cranial neural crest cells after their migration into the pharyngeal arches.
Our last animation shows the migration pathway taken by human cardiac neural crest cells. "The caudal region of the cranial neural crest is sometimes called the cardiac neural crest, since its cells (and only these particular neural crest cells) can generate the endothelium of the aortic arteries and the septum between the aorta and the pulmonary artery (Gilbert 2000)." These cardiac neural crest cells lie above the 7th rhombere of the neural tube and migrate to pharyngeal arches 4 and 6 during the fifth week of gestation. Once the cells enter the truncus arteriosus they generate the septum.
A very unique characteristic of the cardiac neural crest is that when they are replaced by either cranial or trunk neural crest, proper development does not occur. It can thus be determined that "the cardiac neural crest is already determined to generate cardiac cells, and other regions of the neural crest cannot substitute for it (Gilbert 2000)."
The transcription factor Pax3 has been found to be an important component in proper development. "Mutations of Pax3 result in persistent truncus arteriosus, the failure of the aorta and pulmonary artery to separate (Gilbert 2000)." Defects can then also be seen in the thymus, thyroid, and parathyroid glands.
Recent research has shown that neural crest cells might cooperate with one another as they migrate. There may be "subtle communication between these cells through their gap junctional complexes, and this communication may be important for the development of all the structures that are differentiated from neural crest cells (Gilbert 2000)."
