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BMS2.27 Neural Crest (PINTAR) > Neural Crest > Flashcards

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
What molecule serves as a chemoattractant to neural-crest that colonize the gut?
* GDNF ligand
26
What are some abnormalities present at birth in patients with DiGeorge Syndrome (DGS)?
* Cardiac outflow tract & septal defects * Thymus and parathryoid hypoplasia * immune deficiency * Cleft palate * small jaws * Low-set, abnormal ears
27
What is the gene locus for DiGeorge Syndrome?
Chromosome 22q11
28
Deficits are seen in what two tissue types in Digeorge Syndrome?
* pharyngeal arch and pharyngeal pouch derivatives (larynx, pharynx) * neural crest derivatives (thymus, parathyroid, outflow tract cells in heart)
29
What two genes are involved in Digeorge Syndrome?
TBX1 and Crkl
30
Tbx-1 is a downstream target of what signalling pathway?
sonic hedgehog
31
Crkl:
* expressed in neural crest cells * upstream regulator of TGF/FGF signaling * leads to severe defects in cardiovascular patterning
32
Tbx-1:
* 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
What gene is critical to the development of the correct environment for neural crest cells to survive and proliferate in the pharynx?
Tbx-1
34
What are the sequential interactions that can be disrupted to cause DiGeorge Syndrome?
* Mutations in Tbx-1 adversely affect the pharyngeal environment * Mutations in Crkl lead to defects in cardiovascular patterning
35
Phenotype of Fetal Alcohol Syndrome:
* 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
Fetal alcohol syndrome has severe consequences on:
* midline rostral formation
37
How does alcohol cause fetal alcohol syndrome/rostral effects?
* alcohol induces apoptosis of in specific populations of cells in the rostral part of the embryo. * includes neural precursors and neural crest cells
38
The neural crest forms and disperses as a result of activation of:
* a sequential cascade of transcription factor activation initially elicited primarily by specific levels of BMP.
39
Migration of neural crest cells to different destinations is controlled in large part by:
* specific ligand-receptor systems in which secreted ligands function as chemoattractants.
40
Alterations in specific aspects of neural crest morphogenesis can occur in response to mutations that effect:
* the environment through which neural crest cells migrate (e.g. Tbx-1) * the neural crest cells themselves (CrkL).

BMS2.27 Neural Crest (PINTAR) (1 decks)

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