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Developmental And Stem Cell Biolody > Cell migration > Flashcards

Cell migration Flashcards

1
Q

What external cues cause cells to move

A

chemoattractants and ECM gradients

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2
Q

What determines how a cell responds to a stimulus

A

expression of cell surface receptors and signalling proteins

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3
Q

What are the features of a cell displaying front-to-back polarity

A

protrusions such as filopodia and lamellipodia at the front where Rac1 and cdc42 are active
contractions at the rear where RhoA is active
mediate polarity by changing the actin cytoskeleton

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4
Q

What attaches a cell to the underlying matrix

A

focal contacts which are mediated by integrins

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5
Q

What are the two types of cell migration

A

single cell migration and collective cell migration

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6
Q

What are cadherins

A

initiate cell-cell adhesion by providing structural support to cells via links to the actin cytoskeleton. form like-with-like homotypic interactions to prevent mingling of unwanted cells

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7
Q

Give two types of cadherins and where they are active

A

N-cadherins = on neural cells
E-cadherins = in epithelia

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8
Q

What is a key feature of leader cells in collective cell migration

A

presence of a free edge

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9
Q

How are cells kept together in collective cell migration

A

by cadherin cell-cell adhesions and cell-ECM adhesions by integrins to coordinate movement with direction

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10
Q

List 3 examples of collective cell migration

A

primordial germ cells, muscle into developing limbs, gastrulation in amniotes, the neural crest

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11
Q

How do primordial germ cells move by collective migration?

A

PGCs originate in the posterior epiblast and move to the genital ridge expanding from 40 cells to around 8,000. cells are guided by chemokines and stem cell factor which are both expressed in the dorsal mesentary

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12
Q

How do primordial germ cells move by collective migration?

A

PGCs originate in the posterior epiblast and move to the genital ridge expanding from 40 cells to around 8,000. cells are guided by chemokines and stem cell factor which are both expressed in the dorsal mesentary

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13
Q

How does the entry of muscle into developing limbs act as an example of collective migration?

A

limb bud originates from lateral plate mesoderm. muscle precursors from somites migrate into the limb bud and are attracted to it by the hepatocyte growth factors which binds to c-met receptors on muscle precursors s

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14
Q

How does gastrulation in amniotes act as an example of collective migration

A

gastrulation begins with primitive streak formation where the epiblast thickens. anterior to this, there is a mound of cells called hensens node. cells migrate inwards through the primitive streak as a sheet in xenopus. early migrating cells become endoderm, late become mesoderm and cells that remain in the epiblast become endoderm. cells migrate through the node form the anterior endoderm, prechordal plate and notochord

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15
Q

How do cells in the neural crest collectively migrate

A

NC cells detach and migrate during neurulation to differentiate into a wide range of neuronal and non-neuronal cell types

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16
Q

What is EMT?

A

Epithelial cell to mesenchymal cell transition. occurs so that migration can happen. reversible and when the mesenchymal cell reaches its destination, it can revert back to an epithelial cell

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17
Q

List some features of epithelial cells

A
  • line our inner organs
    attach to neighbouring cells by E-cadherin
    similar regular shapes
    have polarity and know which direction is apical
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18
Q

List some features of mesenchymal cells

A

migrating
have non-uniform shapes such as polarisation
not usually attached to neighbouring cells
spindle-like shape
increased contractility and matrix deposition
express N-cadherin and ECM proteins to promote matrix deposition

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19
Q

What are the 3 stages of EMT

A

basement membrane breakdown
cytoskeletal change
loss of cell junctions

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20
Q

What is the role of snail transcription factors in EMT

A

they repress E-cadherin causing a loss of adherent junctions. activate genes encoding matrix metalloproteinases which cause degradation of the membrane. cause alterations in polarity by regulating Rho genes

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21
Q

What is the neural crest?

A

High migratory multi potent population of cells
Forms at the boundary of neural plate and epidermal ectoderm
Differentiate into neural and many non-neural cells
One of the defining features of vertebrates

22
Q

What are somites?

A

Somites are transient repeating block of mesoderm either side of the notochord that appear after gastrulation

23
Q

How do somites arise?

A

From mesodermal cells via mesenchymal-to epithelial transition

24
Q

What do somite give rise to?

A

Spinal vertebrae and ribs
Muscles of the trunk and limbs
The dermis

25
Q

What are rhombomeres?

A

A ser9ies of 7/8 transient compartments of cells that appear as a series of bulges in the vertebrae hindbrain.

26
Q

What are brachial arches?

A

Transient pouches that give rise to most of the connective tissue around the head.

27
Q

Where does the neural crest arise from?

A

The border between the neural plate and non-neural ectoderm. Formation of this border requires intermediate levels of BMPs and also wnt and FGF signalling

28
Q

What is snail2 induced by?

A

Wnts and an intermediate level of BMPs

29
Q

Describe the process of fate mapping and what conclusion it led to?

A

Inject fluorescent dye into an individual trunk neural crest cell in a chicken embryo prior to the onset of migration.
After two days dye is found in melanocytes, adrenal gland, sensory neurons.
Conclusion: Most neural crest cells are initially multi potent. They become more specialised (and proliferate) during migration. Their specification as a particular type of derivatives depends at least in part on signals received during migration.

30
Q

What are the two routes of migration?

A

Dorsolateral pathway
Ventral pathway

31
Q

What are ephrins?

A

Are transmembrane ligand that act through juxtacrine signalling.

32
Q

What do ephrins interact with?

A

Eph receptors. The interaction is bidirectional.

33
Q

What does Eph-ephrins interactions lead to?

A

Leads to repulsion between cells.

34
Q

What does ephrin expression block?

A

Blocks entry of neural crest cells into the posterior of somites.

35
Q

What does contact inhibition of locomotion do?

A

Prevents cells from overlapping but induces cell dispersal.

36
Q

What is complement factor C3a?

A

Neural crest cell secrete it. This acts as chemoattractant (co-attraction) this stops the cluster from dispersing.

37
Q

What happens when there is a mutation in SOX10?

A

The dominant condition, Waardenburg shah syndrome type IVc. This results loss of some neural crest derivatives and leads to:
Interstitial blockages, due to absence of neurons to GI tract
Deafness
Defects in skin, hair and eye pigmentation due to loss of melanocytes.

38
Q

What are uses of directed cell migration?

A

Wound healing
Tissue morphogenesis

39
Q

What are the receptors chemokines signal through?

A

Chemokines receptors= G coupled receptors

40
Q

What can influence directional migration?

A

ECM stiffness- Durotaxis
Ligand density- Haptotaxis
Diffusible ligand density- Chemotaxis

41
Q

What is the process of neural crest formation?

A
  1. Induction and delamination
  2. EMT and N-Cadherin switch
  3. Migration
  4. Specification and differentiation
42
Q

In the epithelial-to-mesenchymal transition what a is the spectrum?

A

Epithelial characteristics- Cells clumped together
Mesenchymal characteristics- Single cells
Intermediate- both characteristics- neural crest

43
Q

What did Abercrombie and Heaysman do?

A

Found that 2 different populations of cell is due to contact mediated locomotion/

44
Q

How did scientists identify that cell-cell contacts polarise migrating NC cells in vitro?

A

Took Xenopus neural crest cells, tagged using GFp and RFP nuclear marker- so can clearly define cells as has a nucleus and GFP. Isolated cell are put in culture- Recorded migration of cell- showed directional movement and have sense of polarity. Cells in centre had no direction

45
Q

How did scientists research contact inhibition of locomotion?

A

NC cells taken from one embryo (red) NC cells taken from another embryo (green) . When neural crest cells collide there is contact inhibition. But if beetween mesodermal cells you’d get yellow- so contact inhibition does not occur between mesodermal and neural crest cells

46
Q

What happens when PCP is inhibited in the neural crest?

A

Forms protrusion at cell-cell contacts and are not contact inhibited.
PCP inhibited NC at the edge of an explant do not migrate with directionality or persistence.

47
Q

What does a loss of PCP signalling cause?

A

A loss in cell velocity- Allows front to back polarity

48
Q

What is PCP needed for??

A

Directional migration and polarity

49
Q

What is attracting neural crest cells to each other?

A

Screened for secreted proteins
C3a- chemoattractant in immune response
Both C3a and C3aR are expressed by NC

50
Q

What does blocking C3a function do?

A

Leads to loss of co-attraction

51
Q

What is mechanotrasnduction?

A

the conversion of mechanical forces to biochemical signal/response E.g force sensed at membrane leads to signal transduction in the cell to change gene expression in nucleus. Classice example is activation of

52
Q

What does mechanical forces do to NC cells?

A
  • trigger and guide NC cell migration
  • Matrix stiffness determines cell fate in differentiation
    How NC sense different forces is not clearly understory

Developmental And Stem Cell Biolody (7 decks)

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