Development of the Neural Crest

Question 1

Levels of BMP regulate nervous system formation from the

Answer 1

Ectoderm

Question 2

BMP near the midline is suppressed by

Answer 2

Noggin, Chordin, and FGF

Question 3

Low levels of BMP allow the development of the

Answer 3

Nervous System

Question 4

The first step of neural crest formation is to become distinct from both the

Answer 4

Adjacent ectoderm and neural tissue

Question 5

The second step of neural crest formation is to begin

Answer 5

Migration

Question 6

The third step of neural crest formation is to

Answer 6

Localize and differentiate

Question 7

We can use quail-chick cell transplantation to create a chimeric embryo that allows us to

Answer 7

Map Neural Crest (NC)

Question 8

The neural crest arises from the

Answer 8

Ectoderm

Question 9

The qual-chick experiment allowed us to identify classic derivatives of the neural crest. What are the three cranial derivatives?

Answer 9

1. ) Neurons and glia of cranial ganglia
2. ) Cartilage and bone
3. ) Connective tissue

Question 10

The qual-chick experiment allowed us to identify classic derivatives of the neural crest. What are the three trunk derivatives?

Answer 10

1. ) Pigment cells
2. ) Sensory Neurons and glia
3. ) Sympatho-adrenal cells

Question 11

What are the levels of BMP for the following tissues?

1. ) Epidermal
2. ) Neural crest
3. ) Neural

Answer 11

1. ) High
2. ) Intermediate
3. ) Low

Question 12

Forms at the boundary where presumptive neural plate meets the ectoderm

Answer 12

Neural crest

Question 13

At this boundary, intermediate levels of BMPs in conjunction with FGF and other molecules induce

Answer 13

“snail” and “border specifier” genes

Question 14

The “snail” and “border specifier” genes, in conjunction with BMPs and Wnts, then induce additional transcription factors that specify the

Answer 14

Neural crest

Question 15

Stimulates c-Kit (pigment cells) and c-Ret (enteric neural precursors) expression on NC cells that have long migratory pathways

Answer 15

NC specifier transcription factor Sox10

Question 16

In the initiation and pathways of trunk neural crest migration, first NC must change from epithelium to

Answer 16

Mesenchyme

Question 17

To change from epithelium to mesenchyme, the NC loses its

Answer 17

6B class of Cadherins

Question 18

The NC then migrates into a space filled with

Answer 18

Hyaluronic acid

Question 19

Some disease conditions have deficiencies in several migratory cell populations such as

Answer 19

Pigment cells, hemopoetic cells, and germ cells

Question 20

Specific ligand-receptor systems are used in

Answer 20

Neural crest migration

Question 21

Different mutations in different strains of mice (called Dominant spotting and Steel) alter pigmentation and also lead to

Answer 21

Anemia and Sterility

Question 22

These mutations encode either a specific receptor on the cell surface of the migratory cells or the ligand for that receptor that is produced by the cells in the

Answer 22

Migratory environment

Question 23

Thus, for germ cells, hemopoetic cells, and NC-derived pigment cells, the tyrosine kinase C-kit receptor (mutated in dominant spotting mutation) on migratory cells binds

Answer 23

Steel factor ligan

Question 24

Produced in migratory pathways used by germ cells, hemopoetic cells, and NC-derived pigment cells

Answer 24

Steel factor ligand

Question 25

Production of ligand in the migratory pathway suggests that Steel peptide functions as a chemoattractant for

Answer 25

Receptor Expressing Cells

Question 26

As in mouse, humans heterozygous for c-Kit mutation have -as well as some deficits in hemopoetic and germ cell migration

Answer 26

Pigment migratory deficits

Question 27

Provides progenitors for enteric nervous system

Answer 27

Migration of neural crest into the gut

Question 28

The major congenital abnormality of the gut -characterized by megacolon

Answer 28

Hirschsprung's Disease

Question 29

Individuals with Hirschprung's disease have a deficiency of enteric ganglia and as a result suffer from

Answer 29

Constipation

Question 30

Two non-linked mouse genes producing megacolon when mutated were also identified and turned out to represent another ligand-receptor pair. What is the: 1. ) Receptor 2. ) Ligand

Answer 30

1. ) c-Ret | 2. ) GDNF

Question 31

c-Ret is expressed in

Answer 31

Neural crest cells

Question 32

GDNF is expressed in the

Answer 32

Gut

Question 33

In both c-Ret and GDNF mutant mice, NC migration is | markedly reduced and NC cells never reach the

Answer 33

Posterior gut

Question 34

The mutation that causes the distal enteric ganglia not to form and results in Hirschsprung's disease is a mutation in

Answer 34

c-Ret

Question 35

Functions as a chemo-attractant as neural crest cells colonize the gut

Answer 35

GDNF

Question 36

Neural crest cells interact with multiple cells/matrix components during

Answer 36

Migration

Question 37

Characterized by deficits seen in the pharyngeal arches and pouches (pharynx, larynx) and also in neural crest derivatives (thymus, parathyroid, etc)

Answer 37

DiGeorge Syndrome

Question 38

Develops as the neural crest enters the structure

Answer 38

Pharyngeal system

Question 39

May be the result of initial failure of the pharynx and/or secondary failure of the neural crest

Answer 39

DiGeorge Syndrome

Question 40

Variable size deletions 1.5-3 MB of human Ch22, which contains over 30 genes, are present in >90% of

Answer 40

DiGeorge patients

Question 41

DiGeorge syndrome is the most common microdeletion in humans with an occurance of

Answer 41

1/4000

Question 42

The region corresponding to the human DiGeorge region, 22q11, was found on mouse chromosome

Answer 42

16

Question 43

Experimentation on mice showed that naturally occuring deltions indicated positive expression of

Answer 43

DiGeorge Syndrome

Question 44

The relevant regions that lead to DiGeorge Syndrome include a gene for the transcription factor

Answer 44

Tbx-1 (A T-Box TF)

Question 45

Developmentally important family of transcription factors -Several mutations in this family are associated with human congenital abnormalities

Answer 45

T-Box gene family

Question 46

Expressed in all cell types of the pharynx at mid-gestation, but NOT in the migrating neural crest cells

Answer 46

Tbx1

Question 47

If Tbx1 is involved in Digeorge syndrome, this expression pattern suggests that deficiencies in NC-derived structures are likely secondary to failure of

Answer 47

Pharyngeal cells

Question 48

When we knock out the Tbx-1 gene in mice, the mutant mice have multiple features of

Answer 48

DiGeorge Syndrome (i.e. cleft palate, low set ears, abnormal aortic arches)

Question 49

Upstream regulators of Tbx-1 include

Answer 49

Sonic Hedgehog (Shh)

Question 50

Bind to 5' regulatory regions in FGF family genes

Answer 50

Tbx-1

Question 51

If FGF is diminished in Tbx1 expression domain, phenotype similar to

Answer 51

Tbx-1 mutant mice

Question 52

Is Tbx1 the only gene involved in DiGeorge syndrome?

Answer 52

No

Question 53

An adaptor protein implicated in TGF-β and FGF signaling -another contributer to DiGeorge syndrome

Answer 53

Crkl gene

Question 54

In contrast to Tbx-1, Crkl is expressed in

Answer 54

Neural crest

Question 55

Absence of Crkl (via gene KO) impairs

Answer 55

TGF/FGF signaling

Question 56

The impaired signaling caused by KO of Crkl leads to severe defects in cardio vascular patterning that are specific to the

Answer 56

Neural crest (pharyngeal derivatives = normal)

Question 57

Implicated in the initial formation of pharyngeal arches and pouches prior to neural crest migration

Answer 57

Tbx-1

Question 58

Teratogenic influence on anterior nervous system and neural crest development due to alcohol intake

Answer 58

Fetal Alcohol Syndrome

Question 59

The third leading cause of mental retardation behind fragile X syndrome and Down Syndrome

Answer 59

Fetal Alcohol Syndrome

Question 60

2-3 oz hard liquor/day and or a single binge drinking | episode during pregnancy can induce

Answer 60

Fetal Alcohol Syndrome

Question 61

What is the incidence of Fetal Alcohol Syndrome?

Answer 61

1/500 - 1/750 children

Question 62

Giving prenatal mice alcohol showed that 12 hours after a single EtOH exposure, there was cell death in the

Answer 62

Anterior neural ridge

Question 63

The mice were then exposed to alcohol at a stage when neural folds were forming and neural crest cells started to migrate. The result was that

Answer 63

NC migration was deficient (Much apoptosis)

Question 64

The alcohol exposure also led to a reduced contribution to

Answer 64

Nasal and maxillary processes

Question 65

Forms and disperses as a result of activation of a sequential cascade of transcription factor activation initially elicited primarily by specific levels of BMP

Answer 65

Neural Crest

Question 66

Migration of neural crest cells to different destinations | is controlled in large part by

Answer 66

Specific ligand receptor systems

Question 67

The ligand in the specific ligand-receptor systems functions as a

Answer 67

Chemoattractant