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Flashcards in Development of the Neural Crest Deck (67):
1

Levels of BMP regulate nervous system formation from the

Ectoderm

2

BMP near the midline is suppressed by

Noggin, Chordin, and FGF

3

Low levels of BMP allow the development of the

Nervous System

4

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

Adjacent ectoderm and neural tissue

5

The second step of neural crest formation is to begin

Migration

6

The third step of neural crest formation is to

Localize and differentiate

7

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

Map Neural Crest (NC)

8

The neural crest arises from the

Ectoderm

9

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

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

10

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

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

11

What are the levels of BMP for the following tissues?

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

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

12

Forms at the boundary where presumptive neural plate meets the ectoderm

Neural crest

13

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

"snail" and "border specifier" genes

14

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

Neural crest

15

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

NC specifier transcription factor Sox10

16

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

Mesenchyme

17

To change from epithelium to mesenchyme, the NC loses its

6B class of Cadherins

18

The NC then migrates into a space filled with

Hyaluronic acid

19

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

Pigment cells, hemopoetic cells, and germ cells

20

Specific ligand-receptor systems are used in

Neural crest migration

21

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

Anemia and Sterility

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

Migratory environment

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

Steel factor ligan

24

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

Steel factor ligand

25

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

Receptor Expressing Cells

26

As in mouse, humans heterozygous for c-Kit mutation have

-as well as some deficits in hemopoetic and germ cell migration

Pigment migratory deficits

27

Provides progenitors for enteric nervous system

Migration of neural crest into the gut

28

The major congenital abnormality of the gut

-characterized by megacolon

Hirschsprung's Disease

29

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

Constipation

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

1.) c-Ret
2.) GDNF

31

c-Ret is expressed in

Neural crest cells

32

GDNF is expressed in the

Gut

33

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

Posterior gut

34

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

c-Ret

35

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

GDNF

36

Neural crest cells interact with multiple cells/matrix components during

Migration

37

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

DiGeorge Syndrome

38

Develops as the neural crest enters the structure

Pharyngeal system

39

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

DiGeorge Syndrome

40

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

DiGeorge patients

41

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

1/4000

42

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

16

43

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

DiGeorge Syndrome

44

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

Tbx-1 (A T-Box TF)

45

Developmentally important family of transcription factors

-Several mutations in this family are associated with human congenital abnormalities

T-Box gene family

46

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

Tbx1

47

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

Pharyngeal cells

48

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

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

49

Upstream regulators of Tbx-1 include

Sonic Hedgehog (Shh)

50

Bind to 5' regulatory regions in FGF family genes

Tbx-1

51

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

Tbx-1 mutant mice

52

Is Tbx1 the only gene involved in DiGeorge syndrome?

No

53

An adaptor protein implicated in TGF-β and FGF signaling

-another contributer to DiGeorge syndrome

Crkl gene

54

In contrast to Tbx-1, Crkl is expressed in

Neural crest

55

Absence of Crkl (via gene KO) impairs

TGF/FGF signaling

56

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

Neural crest (pharyngeal derivatives = normal)

57

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

Tbx-1

58

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

Fetal Alcohol Syndrome

59

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

Fetal Alcohol Syndrome

60

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

Fetal Alcohol Syndrome

61

What is the incidence of Fetal Alcohol Syndrome?

1/500 - 1/750 children

62

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

Anterior neural ridge

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

NC migration was deficient (Much apoptosis)

64

The alcohol exposure also led to a reduced contribution to

Nasal and maxillary processes

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

Neural Crest

66

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

Specific ligand receptor systems

67

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

Chemoattractant

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