Neural Crest Flashcards

1
Q

Levels of what protein regulate nervous system formation from ectoderm?

A

BMP

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2
Q

Low levels of BMP allow:

A

nervous system development

  • BMP is suppressed by chordin, noggin, and FGF at the midline to allow for nervous system development.
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3
Q

What three proteins suppress BMP at the midline to allow for nervous system development?

A

chordin, noggin, and FGF

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4
Q

High levels of BMP allow:

A
  • maintenance of ectoderm development
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5
Q

Intermediate levels of BMP allow for formation of:

A

neural crest cells

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6
Q

Distribution of BMP related to development of the neural tube:

A
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7
Q

What are the major steps in neural crest cell formation?

A
  1. Neural crest cells become distinct from ectoderm and neural tissue.
  2. Neural crest cells begin migration.
  3. Neural crest cells localize in their target tissue and differentiate.
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8
Q

Trunk derivatives of the neural crest:

A
  1. pigment cells
  2. sensory neurons and glia
  3. adrenal cells
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9
Q

Cranial derivatives of the neural crest:

A
  • neurons and glia
  • cartilage and bone
  • connective tissue
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10
Q

Where do neural crest cells form?

A
  • at the boundary where the neural plate meets the ectoderm
    • intermediate levels of BMP present here
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11
Q

What transcription factor initiates formation of neural crest cells from the neural tube in response to intermediate levels of BMP?

A

snail

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12
Q

What transcription factor is the “border specifier” in neural crest cell development from the neural tube?

A

Sox10

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13
Q

What transcription factors make up the transcription factor cascade of neural crest cell development?

A
  1. Snail (initiator)
  2. Sox10 (border specifier)
  3. C-Kit (pigment cells)
  4. C-Ret (enteric nervous system precursors)
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14
Q

What are the first two steps of neural crest migration?

A
  1. Neural crest cells change from epithelium to mesenchyme
    • Lose 6B class of cadherins
  2. Neural crest cells migrate into hyaluronic acid filled space and migrate to their target tissue
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15
Q

Path of migration of neural crest cells:

A
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16
Q

How do neural crest cells change from epithelium to mesenchyme?

A
  • Lose 6B class of cadherins
    • cadherins involved in cell adhesion
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17
Q

What is the receptor and ligand in the migratory pathway of germ cells, hemopoetic cells, and NC-derived pigment cells from the neural crest to their target tissue?

A
  • Receptor:
    • C-Kit, located on pigment cells
  • Ligand:
    • Steel factor, secreted by migratory pathway
18
Q

C-kit:

A
  • tyrosine kinase receptor on germ cells, hemopoetic cells, and NC-derived pigment cells.
  • used during their migration from the neural crest.
  • binds steel factor.
19
Q

What molecule serves as a chemoattractant to germ cells, hemopoetic cells, and NC-derived pigment cells in their migratory pathway?

A
  • steel factor ligand
20
Q

What ligand-receptor system is used for the migration of germ cells, hemopoetic cells, and NC-derived pigment cells from the neural crest?

A
  • ligand: steel factor; chemoattractant
  • receptor: c-Kit; located on cells
21
Q

What is the heterozygous c-Kit phenotype in humans and mice?

A
  • white stripe/patch on forehead and belly
  • defects in hemopoetic and germ cell migration
22
Q

Hirschsprung’s disease phenotype:

A
  • major congenital abnormality of the gut
  • characterized by megacolon:
    • deficiency of enteric ganglia
    • gut cannot empty
    • constipation
23
Q

What ligand-receptor system is used for the migration of neural crest cells to the gut?

A
  • ligand: GDNF; chemoattractant
  • receptor: c-Ret; located on NC cells
24
Q

What is the major mutation that causes Hirschsprung’s Disease?

A
  • a mutation in the c-Ret receptor located on NC cells that migrate to the gut
25
Q

What molecule serves as a chemoattractant to neural-crest that colonize the gut?

A
  • GDNF ligand
26
Q

What are some abnormalities present at birth in patients with DiGeorge Syndrome (DGS)?

A
  • Cardiac outflow tract & septal defects
  • Thymus and parathryoid hypoplasia
    • immune deficiency
  • Cleft palate
  • small jaws
  • Low-set, abnormal ears
27
Q

What is the gene locus for DiGeorge Syndrome?

A

Chromosome 22q11

28
Q

Deficits are seen in what two tissue types in Digeorge Syndrome?

A
  • pharyngeal arch and pharyngeal pouch derivatives (larynx, pharynx)
  • neural crest derivatives (thymus, parathyroid, outflow tract cells in heart)
29
Q

What two genes are involved in Digeorge Syndrome?

A

TBX1 and Crkl

30
Q

Tbx-1 is a downstream target of what signalling pathway?

A

sonic hedgehog

31
Q

Crkl:

A
  • expressed in neural crest cells
  • upstream regulator of TGF/FGF signaling
  • leads to severe defects in cardiovascular patterning
32
Q

Tbx-1:

A
  • transcription factor made in the pharynx under Shh signaling
  • upstream regulator of FGF signaling
  • allows neural crest cells to survive and be maintained in the pharynx
33
Q

What gene is critical to the development of the correct environment for neural crest cells to survive and proliferate in the pharynx?

A

Tbx-1

34
Q

What are the sequential interactions that can be disrupted to cause DiGeorge Syndrome?

A
  • Mutations in Tbx-1 adversely affect the pharyngeal environment
  • Mutations in Crkl lead to defects in cardiovascular patterning
35
Q

Phenotype of Fetal Alcohol Syndrome:

A
  • small head size
  • small brain size
  • neurological (Down’s; Fragile X)
  • Short openings between eyelids
  • Low nose bridge
  • Smooth philtrum (ridge between nose & upper lip)
  • Congenital heart disease
36
Q

Fetal alcohol syndrome has severe consequences on:

A
  • midline rostral formation
37
Q

How does alcohol cause fetal alcohol syndrome/rostral effects?

A
  • alcohol induces apoptosis of in specific populations of cells in the rostral part of the embryo.
    • includes neural precursors and neural crest cells
38
Q

The neural crest forms and disperses as a result of activation of:

A
  • a sequential cascade of transcription factor activation initially elicited primarily by specific levels of BMP.
39
Q

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

A
  • specific ligand-receptor systems in which secreted ligands function as chemoattractants.
40
Q

Alterations in specific aspects of neural crest morphogenesis can occur in response to mutations that effect:

A
  • the environment through which neural crest cells migrate (e.g. Tbx-1)
  • the neural crest cells themselves (CrkL).