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What is considered the fourth germ layer?
neural crest cells
What determines the fate of ectodermal cells?
temporal activities of Wnt and BMP signaling
Where is placodal ectoderm found?
anterior region
What does placodal ectoderm generate?
eyes, nose, ears
What type of cells come from constant high levels of both Wnt and BMP?
epidermis
What type of cells come from initial high levels of Wnt and then high levels of BMP:
Placodal cells
What cells come from constant high levels of Wnt and then high levels of BMP later?
Neural crest cells
What type of cells come from only high levels of Wnt?
Neural cells
What do neural crest cells form?
PNS, some endocrine tissues, and connective tissues
Wnt and BMP together activate what neural crest cell specifier?
Sox 9
Whats the Sox 9 pathway in neural crest cell development?
Sox 9 → Snail —I E-cadherin —I EMT
Sox transcription factor promotes…?
EMT
Activation of snail allows neural crest cells to…?
delaminate
A sox transcription factor also promotes…?
neural plate fate and inhibits epidermal fate
Migration of neural crest cells dorsolaterally over somites leads to…?
pigment cells
Migration of neural crest cells over the neural tube to the anterior half of the somite leads to…?
dorsal root ganglion, part of the PNS
What does ventral migration of somites lead to?
sympathetic and sensory ganglia
Where do attractive cues come from during neural crest cell migration?
their target sites
What prevents neural crest cells from taking wrong turns?
repulsive cues
What do ephrins bind to?
Eph receptors
What do semaphorins bind to?
plexins
Can ephrins bind plexins and semaphorins bind Eph receptors?
no
The segmental arrangement of DRG (sensory neurons) is due to the migration of neural crest cells to…?
anterior halves of the somites
What repulses neural cells from the posterior compartment of the somite?
Expression of ephrin B1
Strong interactions in Ephrin signaling leads to?
bidirectional endocytosis and cell detachment
Repulsion comes from what type of Ephrin interactions?
strong
Attraction comes from what type of Ephrin interactions?
weak
What do cardiac neural crest cells express?
Plexin A2 and Plexin D1
What do PlexinA2 and PlexinD1 in cardiac neural crest cells bind to?
semaphorin 3C
Neural crest cell routes express Semaphorins 6A and 6B which…?
repel neural crest cells
Neural crest cell targets express Semaphorin 3C which…?
attract neural crest cells
True or false: the notochord repels neural crest cells
true
Arrival of neural crest cells in specific locations within the embryo leads to…?
expression of specific genes and differentiation
Once neural crest cells reach their targets, they undergo…?
Mesenchymal-to-epithelial transition
What mediates neural crest cell differentiation?
sox transcription factors
Which morphogen specifies the left side?
BMP Nodal
What morphogen specifies the right side?
anti-BMP cerberus
True or false: Cerberus activates Nodal
false
What motor protein does the clockwise rotation of tissues depend on?
dynein
Loss of function mutation in dynein leads to…?
positions of organs become randomized
Dynein moves the liver to which side?
right
Dynein moves the stomach to which side?
left
The first digit in the forelimb is the most…?
anterior part
Which finger is the first digit and most anterior?
thumb
The last digit is the most…?
posterior
Which finger is the last digit and the most posterior?
pinky
The humerus makes up the…?
stylopod
The ulna and radius make up the…?
zeugopod
The carpals and and digits make up the…?
autopod
In the hindlimb, the stylopod is the…?
femur
In the hindlimb, the zeugopod is the…?
tibia and fibula
In the hindlimb, the autopod is the…?
metatarsals and phalanges
The free limb undergoes regulative development which means…?
the cells are not determined yet
What occurs when your remove the free limb?
a new limb can arise from surrounding tissue
What would happen if you split the limb disc into two or more and place barriers between the split pieces to prevent reunion?
ectopic limbs will generated
What initiates limb development?
production of Retinoic acid from lateral plate mesoderm
What produces RA in the lateral plate mesoderm?
Hox genes
During limb development, RA activates ___ which activates ___ which activates ___which activates which activates ___ leading to…?
Tbx, Fgf10, Wnts, FGF, Fgf10, positive feedback, limb bud outgrowth
What is another name for the lateral plate mesoderm?
Limb mesenchyme
In limb bud growth, Wnt promotes…?
cell division in ectodermal plane
In limb bud growth, FGFs increase rate of…?
distal cell migration
What would happen during limb development if the AER was removed?
limb development stops
What would happen during limb development is and extra AER was added?
wing would be duplicated
What would happen if a non limb mesenchyme was put next to an AER?
AER regresses; limb development ceases
What would happen if the AER was replaced by a FGF bead?
a normal wing would develop
What is the important factor in the AER?
FGF8
What are the important factors in the limb mesenchyme?
Tbx and FGF10
What molecular pathway is found in the mesoderm (limb mesenchyme) and what does it activate?
FGF10 —> RTK —> GTPases —> Transcription factor; Wnt3a
What is the first molecular pathway in the ectoderm ( AER) and what does it activate?
Wnt3a —> Fz —> Dsh —I GSK3 —I b-catenin; FGF 8
What is the second molecular pathway in the Ectoderm (AER) and what does it activate?
FGF8 —> RTK —> GTPases —→ Transcription factor; FGF10
What determines the proximal-distal axis of the limb?
Retinoic acid, FGF and Wnt gradients
Retinoic acid is high in which region of the proximal-distal axis of the limb?
proximal
FGF and Wnts are high in which region of the proximal-distal axis of the limb?
distal
Retinoic acid treatment leads to development of…?
more proximal structures
FGF and Wnt treat leads to development of…?
more distal structures
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