Transcript Chapter 13- The neural crest

The neural crest
Chapter 13- The neural crest
Recall lineages
Ectoderm-skin/nerves
Mesoderm-Blood, heart, kidney, bones
Endoderm- Gut and associated organs
Recall- Ectoderm has three fates
1.Epidermis
2.Neural crest cells
3.Neural tube
Fig. 12.3
Epidermis (skin)
Peripheral neurons,
facial cartilage
Brain and spinal chord
This process is called neurulation
The neural crest
Neural crest cell fate depends largely on where they migrate
The neural crest is a transient structure
Potential cell fates include1. neurons and glia
2. medulla of adrenal gland (produces epinephrine)
3. Pigment cells of epidermis
4. Skeletal/connective tissue of head
Neural crest- four functional domains
1. Cranial- cartiledge, bone, neurons, glia of face
2. Cardiac
3. Vagal- parasympathetic ganglia
4. Trunk- melanocytes (produce pigment); sensory and
sympathetic neurons, medulla
Fig. 13.1
Sensory pathways- conduct info to brain-, spinal cord
A quick review of nerve nomenclature
1. Autonomic nervous system
-“involuntary controlled muscles”- CNS sends signals to smooth muscles of
heart, blood vessels, iris, pancreas liver,
digestive tract, kidney
1.Parasympathetic- -homeostasis of body
systems, originate from hindbrain
2. Sympathetic-fright and flight reactionsoriginate form spinal chord
2. Somatic nervous system-“voluntary controlled organs”- CNS sends signals to striated muscles
communication between various parts of
the body (e.g. thallumus, cerebellum) with
muscles
Figure not in text
The neural crest
A. Start with the Trunk Neural crest
Two major paths taken
Path 1-cells travel under epidermis,
become melanocytes, colonize hair and
skin follicles
Epidermis
Neural tube
Sclerotome
Notochord
Path 2-cells to side of neural tube and
through anterior sclerotome to become
sympathetic and sensory neurons
Fig. 13.2
This is a somite
Note – Sclerotome will become
vertebral cartilage
The neural crest
How do these neural crest cells know where to migrate?
1. Epidermis secrete BMP-4 and BMP-7
- BMP-4 and –7 induce neural crest cells to produce slug and RhoB
- Slug dissociates cell-cell tight junctions
2. N- cadherin expression is also lost then regained once reaching
final destination
3. Ephrin proteins in extracellular matrix guide cells
• Neural crest cells have Eph
receptors
• Trunk sclerotome express Eph
ligand
• Binding of Eph receptor to Eph
ligand interferes with migration
• Thus, Eph proteins tell neural
crest cells where not to go
Neural
Crest
cells
Fig. 13.4
Ephrinin sclerotome
4. Stem cell factor allows continued proliferation
5. Other chemotactic and maintenance factors
The neural crest
•Trunk neural crest cells are pluipotent (can become many cell types)
However, it may be that only certain populations of cells are
pluripotent
• Some transcription factors have been identified that dictate cell fate
Mash-1
Sympathetic and
parasympathetic neurons
Trunk neural crest cell Neurogenin
Sensory neuron
Final cell fate is
determined by final
environment
Fig. 13.6- Fate of a trunk
neural crest cell is
influenced by FGF2 and
glucocorticoids
The neural crest
B. The Cranial neural crest
Like the trunk neural crest cells, these can produce
glia, neurons and melanocytes
But, only cranial neural crest cells can produce
cartilage and bone
Rhombomeres
Recall – the neural tube subdives into forebrain,
midbrain and hindbrain
• The hind brain then further subdivides into
rhombomeres
• Each rhombomere is a territory, each produces
ganglia, but each has a distinct fate
•Rhombomeres sit behind the pharyngeal arches
Pharyngeal arches
Fig. 13.1
Three paths for cranial neural crest cells
Pharyngeal
arches
1
2
The neural crest
Rhombomeres in
hind brain of
neural tube
1. Rhombomere 1+2- to 1st Ph. Arch
2. Rhombo. 4- to 2nd Ph. Arch
3
4
3. Rhombo. 6 to 3rd and 4th Ph. Arch
Fig. 13.7 Rhombomeres 3 and 5 do
not migrate through arches
Fate map of pharyngial arches
contributions to face formation
The neural crest
What determines distinct fates of cranial neural crest cells?
Answer- The combination of hox genes
Evidence
1. Hoxa-2 KO- neural crest cells of 2nd Ph. Arch
transformed into 1st Ph. Arch structures
2. Hoxa-1 and Hoxb-1 double KO- no rhombomere 4
migration
+ retinoic
WT
acid
3. Retinoic acid induces more
anterior expression of certain
Hox genes- - rhombomeres 2
and 3 assume role of
rhombomeres 4 and 5
No ear
Fig. 13.8
How is neuronal diversity achieved??
5 ways1. Blocking BMP signal allows formation of dorsal neural tube
(recall chapter 12)
2. Notch-delta specifies neural fate (not epidermal or glial)
3. Initial location determines neuronal type
4. Migration route further dictates specificity
5. Specific connection made with target organs or other neurons
3 parts described
1. Pathway selection- axons travel along a given route
2. Target selection- axons reach a target, then bind
to specific cells
3. Address selection- axons now refine
interactions- bind to only a subset of possible
targets
A. Hypotheses for pathway selection1. Cell adhesions- Growth cone can adhere to certain cells, but not
others
• Laminin – a glycoprotein which appears to
pave the road for several axonal migrations
• N-CAM
2. Physical barriers- Growth cone can adhere to certain cells, but
not others
3. Labeled pathway hypothesis- in insects, a neuron can precisely
follow the path of a prior neuron
Kallmann syndrome- an infertile man with lack of smell
Reason- a single protien directs migration of both
olfactory axons and hormone-secreting nerve cells
4. Repulsiona. Ephrin (recall Fig 13.4) – Growth cones contain Eph
receptors- binding prevents migration into undesirable
areas
b. Semaphorin proteins- important in directing axon turns
Hypotheses for pathway selection- (Cont.)
5. Diffusible moleculesa. Netrin-1 and –2 are chemotactic
Rat dorsal spine explant
Fig. 13.20
Neuron
Outgrowth
Neutrin producing cell
•Netrins are homologues of the UNC-6 protein in C. Elegans
Loss of Unc-6 prevents
migration of both sensory
(to ventral) and motor (to
dorsal) neurons
Fig. 13.21
Sensory Neuron
b. Slit proteins are repulsive
Motor
WT Neuron
Unc-6 -/-
B. Hypotheses for target selection- 0 min
2 min
Target cells secrete short-range
chemotactic or chemorepulsive
factors
Example- NT-3 attracts axons
C. Hypotheses for address selection-
Fig. 13.25
Growth cone
makes contact
with a cell,
acetylcholine
receptors cluster
on target cell
surface, and a
synapse is formed
6 min
10 min
Fig. 13.24
Additional axons synapse
target cell, but eventually
only one/cell remains