Unit 4 - Lecture 18

Neural crest

a collection of multipotent stem cells located at the side of the neural tube proximal to the epidermal layer after neurulation

The neural crest is found in:

A) only vertebrates

B) only invertebrates

C) vertebrates and invertebrates

D) neither

A) only vertebrates

The neural crest is a transient structure (adults do not have a neural crest) (T/F).

True.

Neural crest cells originate from the

A) non-neural ectoderm

B) dorsal neural tube

C) notochord

D) neural plate

B) dorsal neural tube (ectoderm origin)

Neural crest cells undergo an ….. transition and migrate extensively to generate a huge variety of cell types.

A) mesenchymal to epithelial

B) epithelial to mesoderm

C) mesenchymal to mesoderm

D) epithelial to mesenchymal

D) epithelial to mesenchymal

What is used as a model system for neural crest study?

Chicks

**Central nervous systen** (CNS)

brain and spinal cord.

**Peripheral nervous system**

everything outside of the CNS, divided into:


1. **Somatic** **nervous system**
2. **Auronomic** **nervous system**

Somatic nervous system is involuntary (T/F).

False. The somatic nervous system is voluntary, the autonomic nervous system is involuntary.

Somatic nervous system includes which two nerves?

1. **Afferent** (sensory) **nerves**
2. **Efferent** (motor) **nerves**

The autonomic nervous system includes which three systems?

1. **Sympathetic nervous system** (fight or flight)
2. **Parasympathetic nervous system** (breed and feed, rest and digest)
3. **Enteric nervous system** (governing gastrointestinal tract function).

Neural crest cells can be divided into four main, overlapping anatomical regions:

1. Cranial (cephalic)
2. Cardiac
3. Trunk
4. Vagal and Sacral

**Cranial** neural crest cells

migrate to produce the craniofacial mesenchyme, including cartilage, bone, neurons, glia, **melanocytes** (pigment cells), and connective tissues of the face.

**Cardiac** neural crest cells

extending from the otic (ear) places to the third somites. These contribute to the septum of the heart, form the connective tissue of the wall of the large arteries of the heart, and develop into melanocytes, neurons, cartilage, and connective tissue of the third, fourth, and sixth pharyngeal arches.

**Trunk** neural crest cells

lies from about stomate 6 to the tail and make the **dorsal root ganglia** containing sensory neurons, sympathetic neurons (fight or flight), the medulla part of the adrenal gland, and melanocytes.

**Vegal** and **Sacral** neural crest cells

form the parasympathetic (autonomous nervous system) ganglia of the gut and the enteric nervous system. The vagal (neck) neural crest overlaps that of the head and the trunk (about commits 1-7), and the sacral neural crest is posterior to somite 28.

Which neural crest cells enter the pharyngeal arches and pouches to give rise to thymic cells, the odontoblasts of the tooth primordial, and the bones of the middle ear and jaw?

Cranial

The cardiac neural crest is a subregion of the cranial neural crest (T/F).

True.

Nueral crest cells from different regions are *equivalent/not equivalent* in potency and specificity.

*Not equivalent*. Cranial crest cells can make cartilage, muscle, bone, and connective tissue of the cornea, but trunk cells cannot. 

When trunk cells are transplanted to the head region, they can migrate to sites of cartilage and cornea formation and can form either structure (T/F).

False. They __cannot__ form either structure.

Expression of which gene helps determine specificity of the trunk neural crest?

A) Wnts

B) Nodal

C) Hox gene

D) Sox9

C) Hox gene

Most neural crest cells behave as multipotent stem cells even after they begin migrating (T/F).

True. Like other stem cells, paracrine factors specify more and more committed cell fates.

Multipotent stem cells

cells that have the capacity to self-renew by dividing and to develop into multiple specialised cell types present in a specific tissue or organ.

1\. Which of the following is __**TRUE**__regarding the neural crest? 

A) Neural crest cells have mesodermal origin 

B) Neural crest cells undergo a mesenchymal to epithelial transition 

C) The neural crest is a transient structure 

D) The neural crest is found in both vertebrates and invertebrates 

E) Neural crest cells are stationary  

C) The neural crest is a transient structure 

Specification of neural crest cells begins when?

During early gastrulation.

…. and …. activate a sequential series of transcription factors that progressively specify neural crest cell fate. Reconstitution of these pathways allows the reprogramming of other cell types into neural crest cells.

Wnts and BMPs 

*Epidermis* is specified by:

A) BMP

B) Wnt

C) BMP and Wnt

D) Wnt expression early, BMP expression later.

E) Wnt expression later, BMP expression early.

F) Wnt expression persistence, BMP expression later.

C) BMP and Wnt

*Neural* is specified by:

A) BMP

B) Wnt

C) BMP and Wnt

D) Wnt expression early, BMP expression later.

E) Wnt expression later, BMP expression early.

F) Wnt expression persistence, BMP expression later.

B) Wnt

*Placodes* is specified by:

A) BMP

B) Wnt

C) BMP and Wnt

D) Wnt expression early, BMP expression later.

E) Wnt expression later, BMP expression early.

F) Wnt expression persistence, BMP expression later.

D) Wnt expression early, BMP expression later.

*Neural crest* is specified by:

A) BMP

B) Wnt

C) BMP and Wnt

D) Wnt expression early, BMP expression later.

E) Wnt expression later, BMP expression early.

F) Wnt expression persistence, BMP expression later.

F) Wnt expression persistence, BMP expression later.

Which is the key specifier of neural crest?

A) Sox10

B) Sox9

C) Snail

A) Sox10

Which factors are required for the epithelia to mesenchymal transition?

A) Sox10

B) Sox9

C) Snail

B + C) Sox9 and Snail

Neural crest cells must migrate. What effects their migration?

Environmental cues. Including cells around them, local adhesive cues, lang range secreted factors, and tracks.

Do neural crest cells migrate collectively or individually?

Both collectively and individual.

What signal initiate migration (**epithelial-mesenchymal transition** (EMT))?

Activation of Wnt genes by BMP.

Where are BMPs made?

Dorsal region of the neural tube (below neural crest tissue).

When BMP inhibitor concentration from the … is reduced, BMPs can become active.

notochord.

What happens when the Wnt genes are activated?

This primes the cytoskeleton for cell migration and dissociates the cadherin connections.

Which genes are activated by Wnt signaling to prime the cytoskeleton?

A) PAX3; SP1

B) Rho; Rac GTPases

C) FGFs; SOX2 

D) Sox9;Snail

E) GATA5; HEY

B) Rho; Rac GTPases

Which proteins dissociate the cadherin connections (repress N-cadherin and E-cadherin domain)?

A) BMPs

B) Sox9

C) Nodal

D) Snail-2

D) Snail-2

Neural crest cells display **contact inhibition of locomotion**, this causes what?

Dispersal of cells.

Which two signals cause contact inhibition of locomotion?

1. Non-canonical Wnt signaling


2. RhoA

Certain neural crest cells display **collective migration**. How is this mediated?

1. Low level N-cadherin
2. **C3a**

After early specification and delamination from the dorsal neural tube, neural crest cells migrate along different paths to their specific locations for final differentiation (T/F).

True.

What are the two major pathways for trunk neural crest migration?

1. **Ventral pathway**
2. **Dorsolateral pathway**

Which pathway do early trunk cells follow?

Ventral pathway.

What do the cells following the ventral pathway form?

* Sensory neurons
* Autonomic neurons
* Adrenomedullary cells
* Schwann cells

**Sclerotome**

Place where the Schwann cells travel through (part of the somite that will form the vertebrae).

Later cells follow the dorsolateral pathway. What do they become?

* Melanocytes (travel between the dermis and epidermis).

Ventrally migrating trunk cells can move either between the somites (to form the sympathetic ganglia of the aorta) or through the somites (T/F).

True.

Early trunk cells go between somites, but this pathway is soon blocked by a protein that repels neural crest cells, called?

**Semaphorin-3F**

The receptor for semaphorin-3F on the neural crest cells is?

**Neuropilin-2**.

Only the extracellular matrix of the posterior of each somite allows migration (T/F).

False. Only the extracellular matrix of the __anterior__.

The posterior portion of each somite contains a protein which also repel neural crest cells, called?

**Ephrins**.

The receptor for ephrins on neural crest cells is?

**Eph**

This patterning of neural crest cell migration generates the overall segmented character of the *peripheral nervous system/central nervous system.*

peripheral nervous system

Ventrally-migrating trunk cells that differentiate within the sclerotome become what?

**Dorsal root ganglia.**

Dorsal root ganglia

contain the sensory neurons that relay information to the central nervous system, and glia cells.

Ventrally-migrating cells that continue migrating past the sclerotome become part of:

A) Parasympathetic autonomous nervous system

B) Sympathetic autonomous nervous system

C) Enteric autonomous nervous system

D) A + B

D) A + B

Trunk cells that will colonize the gut (enteric nervous system) are attracted to the digestive tube by which paracrine factor?

Glial-derived neurotrophic factor (GDNF).

Glial-derived neurotrophic factor (GDNF)

activate cell division and induce neural differentiation.

The receptor for GDNF on neural crest cells is?

**Ret**

**Melanoblasts** (precursors to **melanocytes**, the pigment cells) migrate via the *ventrally pathway/dorsolateral pathway*.

dorsolateral pathway.

The transcription factor that specifies melanoblasts is?

MITF

MITF

activates genes responsible for pigment production, specifies travel along the dorsolateral pathway into the skin, and prevents apoptosis of migrating cells.

Mutations in MITF lead to defects. What is an examples?

Dalmatians and American paint horses heterozygous for MITF have spots due to random death of melanoblasts. Melanocytes also induce blood formation in the inner ear, so they have a high frequency of deafness.

Other neural crest-expressed genes lead to defects too. A mutation in the **KIT** gene for example results in what?

Piebaldism

Piebaldism

reduced proliferation of neural crest cells as well as germ cell and blood cell precursors.

2\. _____________ and ________________ are required for the epithelia to mesenchymal transition of neural crest cells.  

A) PAX3; SP1 

B) Wnts; Nodal   

C) FGFs; SOX2 

D) Sox9; Snail 

E) GATA5; HEY2 

D) Sox9; Snail

Which cells are largely responsible for the formation of the head?

Cranial

Cranial neural crest cells migrate from the midbrain and hindbrain anterior to:

A) Frontonasal process

B) Lateral nasal process

C) rhombomere 8

D) Pharyngeal arches

C) rhombomere 8

Rhombomere 8 migrates into the:

A) Frontonasal process

B) Lateral nasal process

C) Pharyngeal arches

D) A + C

D) A + C

What do the pharyngeal arches and the frontonasal process form?

Face.

What are the three major pathways of cranial cell migration?

1. Neural crest cells from the midbrain and rhombomeres 1 and 2 of the hindbrain migrate to the first pharyngeal arch (the mandibular arch).


2. Here they form the jawbones, the incus and malleus bones of the ear, and various nerves.
3. Additional cells enter the head and form the frontonasal process, which is composed of the forehead, middle of the nose, and primary palate.

Rhombomere 4

populate the second pharyngeal arch, which forms;

* the upper hyoid cartilage of the neck
* the stapes bone of the middle ear
* additional nerves

Rhombomeres 6-8

Migrate into the third and fourth pharyngeal arches to form:

* Lower hyoid cartilage
* Contribute to the thymus, parathyroid, and thyroid glands
* Contribute to the aorta and pulmonary arteries.

Rhombomeres 3 and 5

Join streams from rhombomeres 2, 4 and 6.

Cranium

vertebrate skull.

Neural crest cells form most of the **cranium** (T/F).

True.

Intramembranous bones

Bones created by laying down calcified spicules directly in connective tissue without a cartilaginous precursor.

Are cranial bones intramembranous?

Yes.

The front of the head is derived from:

A) Neural crest

B) Mesoderm

C) Neural crest and mesoderm

A) Neural crest

The back of the skull is derived from:

A) Neural crest

B) Mesoderm

C) Neural crest and mesoderm

C) Neural crest and mesoderm

Facial muscles are derived from:

A) Neural crest

B) Mesoderm

C) Neural crest and mesoderm

C) Neural crest and mesoderm

Rates and directions of cranial neural crest cell divisions determine what our face looks like (T/F).

True.

Where does the heart originally form?

Neck region.

**Cardiac neural crest**

In the caudal (posterior) part of the cranial neural crest and gives rise to the endothelium (inner lining) of the aortic arch arteries and the septum between the aorta and the pulmonary artery.

Cardiac neural crest cells are attracted to the region by which gene?

**Fgf8**.

Cardiac cells also form other neck structures, including:

* Thyroid parathyroid
* Thymus glands
* Carotid body

Which gene do cardiac cells express in mice?

Pax3

How do congenital heart defect often occur?

Defects in the neck structures.

Neurons can generate extremely complex neural networks (T/F).

True.

Axons grown via?

Growth cones.

Growth cones

the locomotion apparatus of an axon.

How do growth cones migrate?

via environmental sensing using the same types of signals as migrating neural crest cells. 

Growth cones move by pointed filopodia called?

Microspikes.

The navigation of axons to their appropriate targets depends on guidance molecules in the extracellular environment. What are the major regulator of actin filament dynamics that drive movement.

Rho GTPases

Pioneer nerve fibers

go ahead of other axons and serves as guides. They migrate while embryonic distances are still short and embryonic tissue is relativist uncomplicated.

All pioneer neurons die after follow up neurons reach their destination (T/F).

False. Some die.

The specificity of neuronal connections depends on which three steps?

1. Pathway selection
2. Target selection
3. Address selection