Bio 127 - Section III Organogenesis

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Bio 127 - Section IIIOrganogenesis

• The Neural Crest and Axonal Specification
• Gilbert 9e Chapter 10

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Student Learning Objectives

• You should understand that the neural crest is an
  evolutionary advancement unique to vertebrates.
• a. Led to jaws, face, skull, sensory neural
  ganglia
• b. Transient structure exists briefly at
  neural tube closure
• 2. You should understand that the neural crest is
  specified into four overlapping regions along the
  anterior-posterior axis
• a. Cranial neural crest
• b. Cardiac neural crest
• c. Trunk neural crest
• d. Vagosacral neural crest

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Student Learning Objectives

• 3. You should understand that most cells of the
  neural crest are either multipotent progenitor
  cells or are already determined to a fate.
• a. Large majority of early chick cranial NC can
  form all cranial fates but only 10 of the total
  population that migrates out.
• b. Nearly half of chick trunk NC are restricted
  to one fate
• c. Other cells from chick trunk NC can produce
• 1. sensory neurons
• 2. melanocytes
• 3. adrenomedullary cells
• 4. glia
• 4. You should understand that it is unknown if
  any NC population is a true stem cell, capable of
  generating stem cells or multiple progenitors

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Around the time of neural tube closure...
Neural crest cells migrate laterally and
ventrally from the dorsal side of the tube.
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Usually the migration is a fire drill and all
cells leave the a tube...
Distances can vary from short to very long
migrations.
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Anterior-Posterior patterning of tube extends to
the crest
Cranial NC

• Vagosacral NC

Cardiac NC
Vagal NC
Trunk NC
Sacral NC
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Neural Crest Cell Fates
Cranial Neural Crest Craniofacial Mesenchyme chondrocytes
osteoblasts of head and face
cranial neurons
glia
fibroblasts, face connective tissue
Pharyngeal Mesenchyme thymic cells
odontoblasts of tooth primordia
bone of inner ear and jaw

Cardiac Neural Crest Otic Placode to Third Somite melanocytes
neurons
cartilage
connective tissue
smooth muscle of outflow
connective tissue of outflow
cardiac septal mesenchyme

Trunk Neural Crest Ventrolateral Anterior Sclerotome dorsal root sensory ganglia
sympathetic ganglia
adrenomedullary cells
aortic nerve clusters
Dorsolateral melanocytes

Vagosacral Neural Crest Somites 1-7, Posterior to Somite 28 parasympathetic neurons of gut
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Anterior-Posterior patterning of tube extends to
the crest
Your starting position limits (specifies)
your fate choices and your experiences on the
road choose (determine) the one.
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Figure 10.17 The influence of mesoderm and
ectoderm on the axial identity of cranial neural
crest cells and the role of Hoxa2 in regulating
second-arch morphogenesis
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Figure 10.10 Cranial neural crest cell migration
in the mammalian head
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Cranial Neural Crest
Midbrain osteoblasts of f frontonasal process FGF, BMP, Edn-1, Nppc, Ihh Twist, Snail, Runx2
Head and 1st Arch myoblasts of facial muscles FGF Twist, Snail,

Rhomb 1,2, 3 osteoblasts, incus malleus FGF, BMP, Edn-1, Nppc, Ihh Twist, Snail,Runx2
1st Pharyngeal Arch osteoblasts of jaw FGF, BMP, Edn-1, Nppc, Ihh Twist, Snail,Runx2
neurons of trigeminal ganglion FGF, neurotrophin, GDNF Twist, Snail
neurons of ciliary ganglion FGF, neurotrophin, GDNF Twist, Snail
glial cells FGF, neuregulin, Edn-3 Twist, Snail
fibroblasts, face connective tissue FGF Twist, Snail
odontoblasts of tooth primordia FGF, BMP Twist, Snail, Barx1, Msx1,2

Rhombomere 3, 4, 5 chondrocytesof hyoid FGF, BMP Twist, Snail, Osteopontin
2nd Pharyngeal Arch osteoblasts, stapes of inner ear FGF, BMP, Edn-1, Nppc, Ihh Twist, Snail, Runx2
neurons of facial ganglion FGF, neurotrophin, GDNF Twist, Snail
glial cells FGF, neuregulin, Edn-3 Twist, Snail

Rhombomere 6-8 chondrocytesof hyoid BMP Twist, Snail, Osteopontin
3rd and 4th Arches thymic cells FGF Twist, Snail
thyroid cells FGF Twist, Snail
parathyroid cells FGF Twist, Snail
clavicular tendon FGF Twist, Snail
thymic cells FGF Twist, Snail
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Cardiac neural crest
Pax3 in outflow tract arteries
Contribution to cardiac septum
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Cardiac Neural Crest
Cardiac Neural Crest melanocytes FGF, Steel, Edn-3, a-MSH Twist, Snail, Pax3
Otic Placode to neurons FGF, neurotrophin, GDNF Twist, Snail, Pax3
Third Somite chondrocytes BMP Twist, Snail, Pax3
fibroblasts, heart connective tissue FGF Twist, Snail, Pax3
3rd , 4th, 6th Arches smooth muscle of outflow FGF Twist, Snail, Pax3
fibroblasts, outflow connect. tissue FGF Twist, Snail, Pax3
cardiac septal mesenchyme FGF Twist, Snail, Pax3
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The Trunk Neural Crest
The cells of the Trunk NC can head off one of two
directions
(the other is the ventral pathway)
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Trunk neural crest cell migration
Some individual cells can contribute to multiple
fates
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Trunk Neural Crest
Ventrolateral dorsal root sensory ganglia FGF, neurotrophin, GDNF Twist, Snail
Anterior Sclerotome sympathetic ganglia FGF, neurotrophin, GDNF Twist, Snail
adrenomedullary cells FGF Twist, Snail
aortic nerve clusters FGF, neurotrophin, GDNF Twist, Snail
glia, Scwann cell FGF, neuregulin, Edn-3 Twist, Snail

Dorsolateral melanocytes FGF, Steel, Edn-3, a-MSH Twist, Snail
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Ventrolateral cell migration through anterior
sclerotome only
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Restriction due to the ephrin proteins of the
sclerotome
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Anterior-Posterior patterning of tube extends to
the crest
Cranial NC

• Vagosacral NC

Cardiac NC
Vagal NC
Trunk NC
Sacral NC
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Vagosacral Neural Crest
Somites 1-7 Posterior to Somite 28 parasympathetic neurons of gut FGF, neurotrophin, GDNF Twist, Snail, Phox2b

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Figure 10.8 Entry of neural crest cells into the
gut and adrenal gland
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Figure 10.18 Plasticity and pre-patterning of
the neural crest both play roles in beak
morphology
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Neuronal Specification and Axonal Specificity

• 100 billion neurons in the adult
• 300 billion born!
• All with a single axon, one or a few synapses
• All with a single phenotype, neurotransmitter
• Making the right synapse is critical
• Motor neurons better find a skeletal muscle
• Retinal neurons better find the optic tectum

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Neuronal Specification and Axonal Specificity

1. Induction and patterning of brain region
2. Birth and migration of neurons and glia
3. Specification of cell fates
4. Guidance of axons to specific targets
5. Formation of synaptic connections
6. Competitive rearrangement of synapses
7. Survival and final differentiation by signal
8. Continued plasticity throughout life

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Heirarchical Specification
ectoderm
blocking BMP
epidermis neural crest neuroepithelium
Delta-Notch
neuron glia ependyma
Shh/TGF-B
motor sensory interneuron
Hox genes
jaw forelimb hindlimb tail
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Heirarchical Specification
hindlimb
birthday retinoic acid
columns of terni (CT) medial
motor columns (MMC)
lateral motor columns (LMC)
Lhx-3 TF
cadherins Lim family TF
axial muscles
express FGF-R positive chemotaxis
lateral subdivision medial subdivision
Isl-2, Lim-1 express Eph-A4 repelled by
ephrin-A5 forces them into hamstring
Isl-1, Isl-2 express neuropilin-2 repelled by
semaphorin-3F forces them quadriceps
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Guidance of Axons to Specific Targets
signals in the membranes of cells along the
migratory path
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Guidance of Axons to Specific Targets
Ephrins and semaphorins can cause the growth cone
to collapse
semaphorin 3 expressing cells
semaphorin 3 expressing cells
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Guidance of Axons to Specific Targets
guidance of the growth cone
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Guidance of Axons to Specific Targets
Netrin is a secreted chemotactic signal for axons
Remember DSCAM? 38,016 splice variants in
Drosophila
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Guidance of Axons to Specific Targets
Few neuronal axons cross the midline of the CNS
creating the hemispheres
Robo-3 overcomes Robo-1
Robo-1 is repelled
Slit is secreted
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Guidance of Axons to Specific Targets
BMPs are secreted from targets, different BMP
receptors guide branches to different targets
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Formation of Synaptic Connections
Reciprocal induction
Requires synaptic transmission
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Formation of Synaptic Connections
Multiple axons compete for final innervation
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Survival and final differentiation by signal

• Apoptosis is often a dominant influence
• More than half of the neurons may die regionally,
  two-thirds of the total born!
• This is less consistent across species than most
  neural development events
• 80 of cat retinal ganglion cells die
• 40 in chick
• 0 in fish, amphibians

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Survival and final differentiation by signal

• Neurotrophic factors block default apoptosis
• Huntingtons corea is a loss of Huntingtin
  protein which upregulates BDNF and the survival
  of striatum neurons
• coordinate movement, balance, walking
• Parkinsons disease is death of dopaminergic
  neurons which respond to GDNF and CDNF therapy?

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Continued plasticity throughout life

• Many organisms have behaviors before birth
• We can alter synaptic connections thru life
• Less so when we get older