Transcript Developmental Biology, 9e

Bio 127 - Section III
Organogenesis
The Neural Crest and Axonal Specification
Gilbert 9e – Chapter 10
Student Learning Objectives
1. 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
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
Around the time of neural tube closure...
Neural crest
cells migrate
laterally and
ventrally from
the dorsal side
of the tube.
Usually the migration is a ‘fire drill’ and all cells leave the a tube...
Distances can vary
from short to very
long migrations.
Anterior-Posterior patterning of tube extends to the crest
Cranial NC
• Vagosacral NC
Vagal NC
Cardiac NC
Trunk NC
Sacral NC
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
Vagosacral Neural Crest
Dorsolateral
melanocytes
Somites 1-7, Posterior to Somite 28
parasympathetic neurons of gut
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.
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
Figure 10.10 Cranial neural crest cell migration in the mammalian head
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
Cardiac neural crest
Pax3 in outflow
tract arteries
Contribution to
cardiac septum
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
smooth muscle of outflow
FGF
Twist, Snail, Pax3
fibroblasts, outflow connect. tissue
FGF
Twist, Snail, Pax3
cardiac septal mesenchyme
FGF
Twist, Snail, Pax3
3rd , 4th, 6th Arches
The Trunk Neural Crest
The cells of the Trunk NC can
head off one of two directions
(the other is the ventral pathway)
Trunk neural crest cell migration
Some individual cells can
contribute to multiple fates
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
melanocytes
FGF, Steel, Edn-3, a-MSH
Twist, Snail
Dorsolateral
Ventrolateral cell migration through anterior sclerotome only
Restriction due to the ephrin proteins of the sclerotome
Anterior-Posterior patterning of tube extends to the crest
Cranial NC
• Vagosacral NC
Vagal NC
Cardiac NC
Trunk NC
Sacral NC
Vagosacral Neural Crest
Somites 1-7
Posterior to Somite 28
parasympathetic neurons of gut
FGF, neurotrophin, GDNF
Twist, Snail, Phox2b
Figure 10.8 Entry of neural crest cells into the gut and adrenal gland
Figure 10.18 Plasticity and pre-patterning of the neural crest both play roles in beak morphology
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
Neuronal Specification and Axonal Specificity
1.
2.
3.
4.
5.
6.
7.
8.
Induction and patterning of brain region
Birth and migration of neurons and glia
Specification of cell fates
Guidance of axons to specific targets
Formation of synaptic connections
Competitive rearrangement of synapses
Survival and final differentiation by signal
Continued plasticity throughout life
Heirarchical Specification
ectoderm
blocking BMP
epidermis
neural crest
neuroepithelium
Delta-Notch
neuron
glia
Shh/TGF-B
motor
sensory
interneuron
Hox genes
jaw
forelimb
hindlimb
tail
ependyma
Heirarchical Specification
hindlimb
birthday
retinoic acid
columns of terni (CT)
medial motor columns (MMC)
lateral motor columns (LMC)
cadherins
Lim family TF
lateral subdivision
Isl-2, Lim-1
express Eph-A4
repelled by ephrin-A5
forces them into hamstring
medial subdivision
Isl-1, Isl-2
express neuropilin-2
repelled by semaphorin-3F
forces them quadriceps
Lhx-3 TF
axial muscles
express FGF-R
positive chemotaxis
Guidance of Axons to Specific Targets
signals in the membranes of
cells along the migratory path
Guidance of Axons to Specific Targets
Ephrins and semaphorins can cause the growth cone to collapse
semaphorin 3
expressing cells
semaphorin 3
expressing cells
Guidance of Axons to Specific Targets
guidance
of the
growth cone
Guidance of Axons to Specific Targets
Netrin is a secreted chemotactic signal for axons
Remember DSCAM? 38,016 splice variants in Drosophila
Guidance of Axons to Specific Targets
Few neuronal axons cross the midline of the CNS creating the hemispheres
Slit is
secreted
Robo-1
is repelled
Robo-3
overcomes
Robo-1
Guidance of Axons to Specific Targets
BMPs are
secreted
from targets,
different
BMP receptors
guide branches
to different
targets
Formation of Synaptic Connections
Reciprocal induction
Requires synaptic transmission
Formation of Synaptic Connections
Multiple
axons
compete
for final
innervation
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
Survival and final differentiation by signal
• Neurotrophic factors block default apoptosis
• Huntington’s corea is a loss of Huntingtin
protein which upregulates BDNF and the
survival of striatum neurons
– coordinate movement, balance, walking
• Parkinson’s disease is death of
dopaminergic neurons which respond to
GDNF and CDNF – therapy?
Continued plasticity throughout life
• Many organisms have behaviors before birth
• We can alter synaptic connections thru life
– Less so when we get older