Neural Crest development Flashcards
Tell me where the multipotent stem cells arise from and how they are able to move to their destined location?
- Originate in the dorsal region of the developing neural tube
- Neural crest cells leave the CNS
- Migrate the dorsal neural tube to the periphery of the embryo
- Multipotent stem cells: Give rise to a multitude of cell types
Where do neural crest cells arise from and tell me about their ‘birth’ to the point where they are able to migrate
(A) Neural crest cells undergo an epithelial-to-mesenchymal transition from the dorsal most portion of the neural tube
(B) The neural crest cells can be seen as a collection of mesenchymal cells above the neural tube
(C)
- The neural crest specifies at the border of the neural plate
- and subsequently localizes at the apex of neural folds,
- then neural crest cells delaminate at the point of neural tube closure,
- and finally migrate out of ectodermal tissues
What forms the bone and cartiledge and also contributes to the cranial nerves?
The cranial neural crest migrates into the pharyngeal arches and the face to form the bones and cartilage of the face and neck. It also contributes to forming the cranial nerves
What forms the parasympathetic nerves of the gut and refer to the name and somite number?
The vagal neural crest (near somite’s 1-7)
and the sacral neural crest (posterior to somite 28)
form the parasympathetic nerves of the gut
What number somites does the cardiac neural crest cells arise near and what are they critical in?
The cardiac neural crest cells arise near somite’s 1 through 3;
they are critical in making the division between the aorta and the pulmonary artery (sometimes there is overlap in these regions)
Tell me what the Neural crest cells form and at what somite number this occurs at
Neural crest cells of the trunk (from about somite 6 through the tail) make sympathetic neurons and pigment cells (melanocytes),
and a subset of them (at the level of somite’s 18-24) forms the medulla portion of the adrenal gland (this gland sits on top of kidney and is involved in many endocrine functions such as the release of adrenaline)
Regions of the chick neural crest
What is the hox genes role in this?
Hox gene attenuate (reduce effect of) development potential
What are the two migratory pathways in neural crest cell migration?
Tell me where the cells travel in each of these pathways
Ventral and dorsolateral
Vental: cells travel ventrally though the anterior scleotome
Dorsolateral: Cell travel between the epidermis and the dermis
In neural crest cells that migrate via the ventral pathway, what do they contribute to?
- Sympathetic and parasympathetic ganglia
- adrenomedullary cells
- dorsal root ganglia
In neural crest cells that migrate via the dorsolateral pathway, what do the cells become?
Pigment- producing melanocytes
What do somites arise from?
Sclerotome
What does neural crest cell delamination (delamination is a separation into layers) coincide with?
Neural crest delamination coincides with the separation of neural and surface ectoderms and their fusion at the midline
In the mechanism of neural crest cell migration, what unique adhesion proteins are expressed and where?
- surface ectoderm (E-cadherin)
- neural tube (N-cadherin)
- premigratory neural crest (cadherin-6B)
During neural crest cell migration, what do high levels of BMP and intermediate amount of Wnt do?
High levels of BMP, and intermediate amounts of Wnt (both epidermal) upregulate expression of Snail-2 (and Zeb-2) in the premigratory neural crest cells
What does SNAIL-2 do in this domain where neural crest cell migration is occurring?
Snail-2 proteins repress N-cadherin and E-cadherin in this domain
Where is Cadherin-6B upregulated and what does it activate during neural crest cell migration and why are these activated?
Cadherin-6B is upregulated only in the apical half of premigratory neural crest cells, and activates RhoA and actomyosin contractile fibers for apical constriction and the initiation of delamination
What happens when neural crest cells make contact with one another?
When neural crest cells contact one another, they experience contact inhibition, during which they will stop, turn, and migrate away in the opposite direction
NB. Contact inhibition is a process of arresting cell growth when cells come in contact with each other. As a result, normal cells stop proliferating when they form a monolayer in a culture dish. Contact inhibition is a powerful anticancer mechanism that is lost in cancer cells
Whats RhoA and Rac1?
Two members of the family, Rac1 and RhoA, can show opposite behaviors and spatial localisations, with RhoA being active toward the rear of the cell and regulating its retraction during migration, whereas Rac1 is active toward the front of the cell.
Tell me about the contact inhibition of locomotion
- “kiss and run” process this is known as where the cells touch then move straight apart
- Reorganise actin and actomyosin network and this helps the cells start their migration
What does the collective migration of neural crest cells require and what is this mediated by?
Requires some amount of cell-to-cell adhesion, which is mediated by a low-level N-cadherin expression (blue receptors)
What do neural crest cells arise from? What do they give rise to?
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.
Collectively migrating neural crest cells secrete what? What does this ensure?
Collectively migrating neural crest cells secrete an attractive signal (Complement 3a, C3a) to ensure that neural crest cells continually grow towards each other
The pattern of migration by the group of neural crest cells has what? What is this due to?
The pattern of migration by the group has a collective direction due to ongoing contact inhibition among the cells at the leading edge
Contact of inhibition in neural crest cells is represented by what?
Contact of inhibition is represented by the differential activation of Rho GTPases
During neural crest cell migration, what do the cells sense that helps steer migration?
- Repulsion and attraction tell cells to stay in given environment or to move on to their right location, this guides neural crest cells during their migratory path
- Gradient diffusive manner and generally they are morphogenes
Tell me about the “chase and run” model for chemotactic cell migration. Mention any proteins when necessary
A ventrally positioned placode (blue cells) attracts the leading edge of the cranial neural crest stream via SDF1 (CXCL12)-CXCR4 signaling (the “chase”).
The cranial neural crest contacts the placode, triggering contact inhibition that pushes the placode forward (the “run”)
What yields forward migratory movement of both placodal and cranial neural crest cells?
(A) A ventrally positioned placode (blue cells) attracts the leading edge of the cranial neural crest stream via SDF1 (CXCL12)-CXCR4 signaling (the “chase”). The cranial neural crest contacts the placode, triggering contact inhibition that pushes the placode forward (the “run”)
(B) Internal molecular events and resulting cellular behaviors that yield forward migratory movement of both placodal (blue) and cranial neural crest (red/yellow) cells
What does the placode help form?
The bone of face and head but also the cranial nerves
What does CXCR4 allow hematopoietic cells to migrate to?
The bone marrow
What family is Rac1 and RhoA part of?
Rho family of GTPases
And they are intracellular transducers regulating signalling pathways which control cytoskeleton organisation, transcription and cell proliferation
Simplification of the Chase and run model
- Now, using embryonic cells called ‘neural crest cells’ (which are similar to cancer cells in term of their invasive behaviour) and placode cells which are the precursors for cranial nerves (the equivalent to healthy cells) researchers at UCL have started to unravel this process.
- They have found that when neural crest cells are put next to placode cells they undergo a dramatic transformation and start ‘chasing’ the placode cells.
- At the same time placode cells exhibit ‘escape’ behaviour when contacted by neural crest cells.
- The chasing behaviour depends on the production of small chemical molecules by the placode cells that attracts neural crest cells toward them.
For the chase and run model give example(s) for the chemorepellants and chemoattractants expressed by the placode cells
Chemorepellents: Semaphorins/ ephrins
Chemoattractant: SDF1
Summary
- Neural crest cells are specified at neural tube closure
- They are a multipotent population of cells capable of attaining a variety of terminally differentiated fates
- They migrate to their destinations
- Structures they contribute to correspond to their position along the AP axis
- Developmental potential is often greater than the presumptive fates
- During migration, there exact differentiation pathway will depend upon the signals they receive
- Consider development as a timed process and understand timing of each event
