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BSC Zoology - Developmental Neurobiology > Lecture 16- Neural crest II (migration and differentiation) > Flashcards

Lecture 16- Neural crest II (migration and differentiation) Flashcards

1
Q

What determines where neural crest cells migrate and what types of cells they form?

A

-the target sites and the cell types formed depend on the axial (rostrocaudal) level

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2
Q

What are the four divisions of the axial (rostrocaudal) level along the neural tube?

A
  1. Cranial
  2. Vagal
  3. Trunk
  4. Sacral
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3
Q

What are the 5 methods to study neural crest migration?

A
  1. Surgically remove defined regions of the neural crest, and then determine which structures fail to develop
  2. Construction of chick-quail chimeras
  3. Label pre-migratory cells with fluorescent dyes or radioactive substances
  4. Intrinsic markers of neural crest cells, including localization by immunohistochemistry or in situ hybridization
  5. Transgenic animals expressing reporter genes -Combinations of the above techniques can be used answer particular questions.
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4
Q

What are the advantages/disadvantages of method 1: Surgically remove defined regions of the neural crest, and then determine which structures fail to develop?

A
  • Advantages: shows the importance of particular regions of neural crest
  • Disadvantages: can’t see how the cells get there, or if other cells compensate for the loss of regions. Depends on high level of skill
  • the first method used, cut out bits of the neural crest and see what doesn’t develop
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5
Q

What are the advantages/disadvantages of method 2: Construction of chick-quail chimeras?

A

Advantages: Can identify cells during migration (using fixed embryos). Cells are permanently identified.

Disadvantages:

  • can’t imagine live cells during migration (using fixed embryos)
  • Transplantations are difficult and somewhat variable.
  • also look at sections of the embryos
  • if you stop the embryo during development= so can see where they are
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6
Q

What are the advantages/disadvantages of method 3: Label pre-migratory cells with fluorescent dyes or radioactive substances?

A
  • Advantages: Can image the cells in live embryos. Can label a variable number of cells (1 cell to hundreds or more). Can label different groups of cells or cells in precise locations (fate maps). Very useful for short- term labelling.
  • Disadvantages:
  • The labels are not permanent and are diluted out of the cells over time. -1970s -match with quail and chick chimeras
  • can image cell in live embryos

more notes:

  • can label in different colours and different groups of cells
  • it is short term, dilute out of the cells over time as they divide, daughter cells have less and less with each division
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7
Q

What are the advantages/disadvantages of method 4: Intrinsic markers of neural crest cells, including localization by immunohistochemistry or in situ hybridization?

A

Advantages:

  • Label specific genes or populations of neural crest.
  • Can also use antibodies to other markers concurrently (eg look at proliferation or cell death).
  • Can use to see how specific neural crest genes are affected following experimental manipulation.

Disadvantages:

-can only label fixed tissue (no live imaging).

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8
Q

What are the advantages/disadvantages of method 5: Transgenic animals expressing reporter genes?

A

Advantages:

  • Can track cells using live imaging.
  • Can permanently label cells using some approaches.

Disadvantages:

  • Need to make/have the appropriate transgenic.
  • Permanent transgenic more feasible in certain species (mice, zebrafish).
  • Can make transient transgenic chick and Xenopus.
  • the only live imaging and it is also permanent, hard to do
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9
Q

How do neural crest cells from different rostro-caudal levels migrate and what do they give rise to?

A
  • Neural crest cells from different rostro-caudal levels:
  • Follow different migratory pathways
  • Give rise to different derivatives
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10
Q

Which neural crest cells migrate first?

A

-cranial region neural crest cells

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11
Q

Which neural crest cells migrate last?

A

-sacral region neural crest cells

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12
Q

In which order do the neural crest cells form and migrate?

A
  • neural crest cells form and migrate in a rostrocaudal wave
  • cranial, then vagal, then trunk, and lastly sacral region neural crest cells form and migrate
  • this is due to the rostrocaudal wave in which the neural tube closes
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13
Q

What type of tissues do cranial neural crest cells give rise to?

A
  • neurons and glia and cranial ganglia
  • cartilage and bones
  • connective tissue
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14
Q

What type of tissue do trunk crest neural cells give rise to?

A
  • Pigment cells
  • Sensory neurons and glia
  • Sympatho adrenal cells
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15
Q

What type of cells do cranial neural crest cells give rise to?

A
  • migrate first
  • cranial sensory glia (together with placode cells)
  • parasympathetic ganglia
  • Schwann cells
  • cartilage and bone
  • smooth muscle
  • connective tissue
  • cornea
  • teeth
  • pigment cells (melanocytes)
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16
Q

What type of cells do vagal neural crest cells give rise to?

A
  • cardiac outflow tract septum
  • ventricular septum
  • enteric neurons and glia
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17
Q

What type of cells do trunk neural crest cells give rise to?

A
  • sympathetic ganglia
  • dorsal root ganglia
  • adrenal chromaffin cells
  • schwann cells
  • pigment cells
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18
Q

What type of cells do vagal neural crest cells give rise to?

A
  • parasympathetic ganglia
  • enteric neurons
19
Q

Cranial neural crest, what does it form: details?

A
  • form bone, cartilage and connective tissue in the head and neck
  • the entire facial skeleton and much of the skull, including the upper and lower jaws, the palate and hyoid bone
  • dermis, smooth muscle of the skin
  • smooth muscles of blood vessels forming the aortic arch and the outflow tract of the heart (cardiac neural crest)
  • connective components of striated muscle and glands in the head
  • some endocrine cells, e.g parafollicular cells of the thyroid
20
Q

Do placodes only produce neurons?

A
  • yes
  • glia are all from neural crest cells
21
Q

What can happen if there are prblems on the development of cranial neural crest?

A
  • can lead to caniofacial defect
  • e.g. Treacher Collins syndrome: very rare, caused by a failure of the neural crest migrating to branchial arch 1 to survive (Tcof1 mutation), not enough of the migrating neural crest cells survive
  • also cleft lip and palate:most common
  • jaw malformation (micrognathia)
  • these are not always due to neural crest cells problems but they can be involved
22
Q

How are cranial ganglia formed?

A
  • Cranial neural crest together with placodes form cranial ganglia.
  • There are 2 sorts of cranial ganglia, sensory ganglia (associated with cranial nerves) and parasympathetic ganglia.
23
Q

What can placodes give rise to?

A

-Placodes give rise to some neurons in sensory cranial ganglia and several other structures

24
Q

What are placodes?

A

-specialised (thickened) regions of ectoderm

  • develop from ectoderm
  • induced by growth factors, different ones with different placodes
  • get expression of genes, gets thicker
  • two ways in which they develop=
  • some invaginate (left) and
  • on the right= undergo process of delamination (change from epithelial cell type and coming into the mesenchyme, don’t go very far, form a ganglion under the ectoderm
  • Cells from the placodes enter the mesenchyme and combine with neural crest cells to make ganglia.
  • Neurons in the cranial sensory ganglia arise from:
    (a) placodes
    (b) neural crest
  • Glia in the cranial ganglia arise from the neural crest.
25
Q

What can neurons be made from?

A

-neural crest and placodes

26
Q

Cranial neural crest cells give rise to to glia within ganglia and Schwann cells along nerves? true/false

A

true

27
Q

What are the details about vagal neural crest cells and their derivatives?

A
  • Somites 1-7: different targets:
  • Enteric neural crest (neurons and glia)
  • Cardiac neural crest: outflow tract of the heart (mesenchymal: smooth muscle and connective tissue)
  • Connective tissues in branchial arches (overlap with cranial neural crest)
  • Ganglia (neurons and glia)
28
Q

What influence does neural crest have on cardiac development?

A
  • Cardiac neural crest contribute to connective tissues in the outflow tract and ventricular septum
  • Defects in the cardiac neural crest cause outflow tract abnormalities

T-his can be part of a larger defect in cranial (mesenchymal) derivatives, eg DiGeorge syndrome

-Can be caused by a problem in the neural crest themselves, or in the adjacent tissues.

29
Q

Which parts of the neural crest give rise to the enteric system?

A
  • Enteric neural crest give rise to enteric neurons and glia (enteric nervous system) along the gut.
  • nerons and glia along the gut
  • controls the motility of the gut and secretion
  • The vagal neural crest contribute most of the neurons and glia, the sacral neural crest a small amount.

Defects in the migration of vagal enteric neural crest causes Hirsprung’s disease, these cells have to migrate the longest distance

30
Q

Why is it difficult for neural crest cells to migrate along the gut?

A
  • the gut is growing as the neural crest cells are migrating
  • have to migrate fast to get to the end
31
Q

What is Hirschprung’s disease?

A

-congenital aganglionisis

  • occurs if neural crest cells fail to get to the end of the gut (the anal end)
  • the neural crest cells allow for peristalsis and here don’t have it
  • so constricted gut constantly, completely constipated
  • get mega colon
  • have to undergo surgery or fatal
  • mega colon= normal neural crest cells migration up to there so have enteric neurons
  • it is the region that is constricted, there no enteric neurons
32
Q

What are the details about trunk neural crest and their derivatives?

A
  • Trunk neural crest arise from somite levels 5-28 (last somite).
  • Begin migration after cranial and vagal, but before sacral crest cells
  • Trunk neural crest migrate along two major pathways:
  • Ventral (between and through somites)
  • Dorsolateral (underneath the ectoderm)
33
Q

What are the two major pathways along which the trunk neural crest cells migrate?

A
  • Ventral (between and through somites)
  • Dorsolateral (underneath the ectoderm)
  • ventral go first
  • the ones that come later are in the dorsolateral pathway (mostly pigment cells)
34
Q

What do the ventrally migrating trunk neural crest cells form? (5)

A
  • Sympathetic ganglia (neurons and glia)
  • Dorsal root ganglia (neurons and glia)
  • Schwann cells along nerves
  • Melanocytes
  • Adrenal chromaffin cells
35
Q

What do dorsolaterally migrating trunk neural crest cells form?

A
  • become melanocytes.
  • these cells migrate after the ventrally migrating cells.
36
Q

What are the details about the sacral neural crest and its derivatives?

A
  • Sacral neural crest arises from the neural tube caudal to the last somite.
  • Begin migration last Sacral neural crest give rise to:

a )Neurons and glia in parasympathetic ganglia

b) Enteric neurons in the colon

37
Q

How do cells migrate, and migrate directionally?

A
  • It is more complex in three dimensions, cells can have multiple lamellipodia/processes.
  • Neural crest cells express many cell surface receptors to allow them to interact with their environment.
  • Downstream signalling from these receptors affects the migration and direction of migration of the cell.
38
Q

What are the 7 mechanisms involved in neural crest migration?

A
  1. Chemoattraction
  2. Chemorepulsion
  3. Cell-matrix adhesion
  4. Cell-cell adhesion
  5. Matrix metalloprotease activity
  6. Contact inhibition of locomotion
  7. Growth factor signalling
    - have to know 1 example of each
39
Q

What are the basis for neural crest cell migration?

A
  • Neural crest cells express receptors for various kinds of ligands in environment.
  • Activation of the receptor affects various intracellular signalling pathways.
  • This in turn affects many processes including adhesion to particular substrate, and ultimately controls whether the cell migrates and the direction a cell migrates.
40
Q

What is the example of chemoattraction in neural crest cell migration we have to know?

A
  • SDF1 is a chemokine(=chemoattrant), a small secreted protein, that binds to the G-protein coupled receptor Cxcr4 to mediate chemoattraction
  • Cxcr4 is expressed by Xenopus cranial neural crest cells.
  • Sdf1 is expressed by the mesenchyme in front of the neural crest.
  • neural crest cells follow the gradient to the source

evidence:

-if knock out Sdf1 or Cxcr4 then have no migration

41
Q

What is the example of chemorepulsion in neural crest migration we have to know?

A
  • chemorepulsion regulates chick and mouse trunk neural crest migration
  • chemorepulsion regulates migration in the ventral pathway through the somites (dorsal root ganglia), and in the dorsal pathway
  • the dorsal root ganglia are segmental (thanks to the chemorepulsion)
  • development of the dorsal root ganglia is linked to somite development
  • migration occurs selectively in the rostral half of the somite and in the space between the somites.

-Class 3 Semaphorins are expressed in the posterior half of the somites and neuropilin 2 is expressed by neural crest

42
Q

What are the secreted proteins and recptors involved in the chemorepulsion example?

A
  • Class 3 Semaphorins are expressed in the posterior half of the somites and neuropilin 2 is expressed by neural crest
  • Class 3 Semaphorins are secreted proteins that bind to Neuropilin receptors to inhibit migration.
43
Q

What do class 3 semaphorins do?

A

-inhibit neural crest migration into posterior somite halves

44
Q

What is some evidence for the chemorepulsion example?

A
  • when don’t have the neurophilin2: don’t get proper migration
  • if you knock out sempahorin 3 F: then don’t have the segmented pattern of migration

BSC Zoology - Developmental Neurobiology (32 decks)

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