Bio 5620- Vertebrate Development: neural crest cells and PD axis of limb development

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 which then stop 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 if an 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