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DB3 > Mechanisms Of Development > Flashcards

Mechanisms Of Development Flashcards

1
Q

Mammlian cell movement

A

Move by crawling (except sperm and other rare exceptions)

Broad and flat lamellipodium at front of sheet
Front edge of lamellipodium is full of actin. - relatively short and branched
-new strand of actin is nucleated from Arp2/3 on the side of another

New filaments constantly grow forwards and push against membrane - results in pushing out of a flat plate

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2
Q

Leading edge autonomy

A

Leasing edge is autonomous
Once the actin polymerisation proteins are made they Don’t need to talk to nucleus again for growth of leading edge

Can remove lamellipodium and it will still move

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3
Q

Leading edge tug of war

A

Direction in which cell moves is determined by tug of war

Lamellipodium extends out one way and another at cell front
Then myosin contraction at back end of cell pushes contents forward one of these 2 ways depending on which one is stronger whichever doesn’t slip

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4
Q

Germline separation

A

Promordia are separated early in development in animals

Before gastrulation and hide at top of yolk sac during all the soma rearrangements (gastrulation, neurulation)

Then return and colonise gonads

Gonads form next to mesoneohros and then go down to pelvic level (or done more for scrotum)

Need to move to migrate to these regions

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5
Q

Guidance cues for primordial germ cells

A

Stream into embryo and colonise genital ridge
Pathway can be shown by particular factors they like to grow on/in

Pathway expresses SCF
Germ promordia have kit receptor
Induces lamellipodia in direction of SCF gradient

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6
Q

Kit gradient and skin pigment

A

See marine cells (part of somite) produce Steel (membrane bound ligand for Kit)

Some neural crest cells express kit receptor tyrosine kinase before leaving neural tube
Migrate along the steel expressed by the dermatome-derived dermal fibroblasts - attracted to this and integrate in
Then once this happens - dermal cells turn off steel production
But epidermis (outer layer) cause the neural crest cells that have migrated to dermis to be attracted to top of dermis

Steel signalling is needed for melanocyte survival (may be in elidermis? Seems likely from attract statement or not) except in nevi and melanoma
These cells go in to become differentiated branched melanocytes
Create protective pigment and fan out above stem cells to protect them from UV

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7
Q

Melanoma metastasis danger

A

In melanoma the melanocytes may revert to this migratory state - gigeing metastasis risk

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8
Q

Kit mutations and neural crest migration in mice

A

Cause unlimbered latched at furthest migration points for these neural crest cells (belly)
Run out of signal strength before reaching it I think

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9
Q

The enteric nervous system

A

Longest crest migration

Nervous tissue embedded in gut tissue layers
Neural cell bodies in this gather in plexus
Cables of axons connect these plexuses/i
Come from neural crest cells from somites 1-7 (cervical)

Gut is invaded at neck level and migrate all the way through

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10
Q

Enteric nervous system migration story

A

Neural crest cells invade at neck
-Migrate to foregut - become ENCCs (enteric neural crest derived cells)
-Migrate down to gut - ENCCs pause at caecum (not Present in humans)
-Migrate again - settle and make neurons and glia
-Growth cone migration (axon building ig)
ENS COMPLETE

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11
Q

Signalling mechanism for ENS migration

A

EDN3 expressed along whole gut
Some in oesophageal
But more in stomach
Even more in hindgut
Higher levels further in incentivises moving further in

(GDNF is also expressed in stomach making it more attractive to cells w right receptors)

As cells move down
Some left behind in early gut
GDNF expressed even further down now after this to make going further more attractive

Cells remain connected during this - COLLECTIVE CELL MIGRATION

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12
Q

Reasons for for collective cell migration

A

Staying connected could be for reasons:
-sharing navigation - instead of taking info from just one cell - take average of front cells. - reduced noise ig
-could also be like children attached after school - keeps them all moving the same even if some go off a bot

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13
Q

Mutants for ENS migration

A

Hypoganglionosis - fewer neurons than eusal through whole ENS

Colonic aganglionosis - no ganglia in colon (hindgut area)

Total intestinal aganglionosis - no ganglia past stomach

What to get from this:
Multiple components in this system
Something missing/major problem - can lose entire swathes of ganglia
Smaller things wrong- can get various ranging issues

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14
Q

Issues with missing ENS ganglia

A

Ganglia control peristalsis
Having missing ones is bad
In colonic aganglionosis-no peristalsis in colon - can get severe constipation - needs surgical intervention

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15
Q

Growth cone basic info

A

Once neuronal cells have settled
Axons grow out and connect to other neurons’ dendrites
Growth cone is at leading end of axon
Leading edge of growth cone resembles lamellipodia
Also have Filipinos - work similar to lamellipodia but extend long and thin instead of wide

If growth cone contacts sticky things they stay contacted
Growth cones turn at boundaries

Signalling molecules can bias movement of these extensions in the growth cone leading edge and hence control axon growth direction

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16
Q

EDN3 and GDNF signalling in neural crest settling

A

EDN3 binds EDNRB TM receptor
Is anti migratory and pro proliferation signalling in cell

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17
Q

Repulsive substrates and growth cones

A

Repulsive substrates in regions where neurons must not grow
Cause growth cones to collapse (flat lamellipodia and long Filopodia disappear)
Keep them running in right place
Contain repulsive molecules

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18
Q

Growth cone collapse induced

A

Ephrin

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19
Q

Ephrin growth cone repulsion action

A

Eph receptors bind Ephrin

If no Ephrin is bound - Eph binds nothing in cell
But when Ephrin is bound Eph can bind Ephexin intracellularly

Ephexin unbound by Eph:
-promotes Rac phosphorylation - pushes it into GTP bound form - causes building of protrusive actin in lamellipodia
-also does this to cdc42 - promoted gtp form - promoted filopodia from actin building promotion

Ephexin is bound by Eph:
It instead phosphorylates Rho
This promotes covering of actin by myosin
Myosin contracts
Causes collapse of structures

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20
Q

Collapse induction use in defining paths

A

If just strip of attractive molecules
Easily missed by things not already on the path

But by surrounding the pathway with repulsion can keep cells within the pathway boundary
This together with attractive pathway increases effectiveness a lot

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21
Q

Collapse inducing Ephrin in sorting retinal axons in binocular vision

A

Binocular vision means overlap of the field of vision of both eyes

Neurons that need to go to one side of brain express Eph that can see the boundary -stay on that side - ipsilateral path

Neurons that go to the other side don’t express this Eph so can’t see boundary and so are free to cross to other side (contralateral path)

This occurs with both eyes - diagram helpful

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22
Q

Collapse inducing Ephrin in sorting retinal axons in more general vision context

A

All neurons from one side of an eye and the other side run together within the optic nerve towards the brain before splitting up again

Need to keep them sorted in this order for vision to be processed right
So different neurons express different levels of Eph
And diff parts of brain express diff levels of Ephrin
More Eph = more sensitive to Ephrin
-neurons w low Eph don’t mind where on gradient they are - so get barged to high ephrin gradient location
-intermediate levels want to be at lower levels more than the low Eph ones but less than the higher Eph ones so end up in intermediate ephrin place
-high Eph neurons really don’t like ephrin so stay at lowest part of gradient

COMPETITIVE SORTING SYSTEM

23
Q

Epithelia basic

A

Primitive structures
Basal animals are essentially bags of epithelium with specialisation on the side
Placazoa - dominated by epithelia

First structure made in animals is trophectodern - and epithelium

24
Q

Plant method for changing shape tissue shape

A

Cells stay in same relative positions to each other and cells themselves deform
Common in plants as they don’t have much cell movement

25
Q

Animal way of changing cell sheet shape

A

Don’t really have elongating cells
So instead:
Neighbour exchange:exchange neighbours in. This way they transform the cell sheet shape
Boundaries in one direction in tissue are shrinking while boundaries in another direction lengthen

Short and fat to long and thin

26
Q

Notochord shape change in Corella inflata (chordate)

A

Starts out as heart shape (“pointy” end anterior)
Cells in notochord change neighbours to change from short dumpy form to long rigid form needed for swimming in tadpole form

27
Q

Convergent extension mechanism

A

Imagine hexagons tiled
A left B top D right C bottom
Boundary between A and D shrink to a point
New boundary forms between B and C
B and C boundary lengthens -become neighbours
A and D boundary is lost. - no longer neighbours

28
Q

Ways of making tubes

A

Axial invagination
Orthogonal invagination
Evagination
Cavitation
Wrapping

29
Q

Axial invagination

A

Imagine inflated ballon
Finger pushed into it
But if surface is pushed down to make indentation
Can happen at single cell or multicellular levels

V common and one of evolutionarily earliest ways

30
Q

Orthogonal invagination

A

Long valley dips down
Neighbour exchange at top - top of valley closes off
Orthogonal because axis of tube is parallel to invagination

Neural tube formation

31
Q

Evagination

A

Opposite of invagination

32
Q

Cavitation

A

Process of fluid filled cavity forming inside the morula (cavity is the bladtocoel)
Forming blastocyst

33
Q

Wrapping

A

Cell sheet wraps around to surround a lumen

34
Q

Changing cell shape

A

Individual cell shape changes drive overall shape change of sheet

Apical end constructed by myosin/actin contraction
Displaces cytoplasm basally
Makes cell into wedge shape
If some cells do this - wedge formed in some cells
Because all these cells in the sheet are connected forces a change in entire sheet -curve?

35
Q

Orthogonal invagination of neural tube

A

Cells at bottom of neural tube
Undergo APICAL constiction to bend sheet there one way
Cells at top of tube undergo BASAL constriction to bend it the other way

This forms the shape of the tube
Needs prior patterning if the cells

Then neighbour exchange seals the top - medically directed pressure from flanking ectoderm ushers the bits at top together

36
Q

The need for fusion of cell sheets

A

Hollow sphere with no holes - genus is 0 (eg cnidarian body plan)

But in organism with holes - need to cut and join in order to go from genus 1->0

37
Q

3 ways of fusing

A

Wound healing

Tube connection

Apical sided meet

38
Q

Wound healing

A

Edges of sheet move together and fuse
Scar prone - sealed with scar tissue in adults to prioritise barrier function - fetuses prefer scarless healing

39
Q

Tube connection

A

Cells meet from ends of formed tubes from invagination meet, stick, and then there is a rearrangement - some cells let go of neighbours and join onto new ones to fuse tubes together

Basal sides meet

40
Q

Apical sides meet

A

Similar to tube connection
Except that it is the apical sides that meet

41
Q

Secondary palate formation

A

The primary palate (median palatal shelf)
And lateral palatal shelves
LPS grow inward and fuse to form secondary palate
Separating the nasal cavity from the mouth

Edges of the LPS epithelia meet
The touching edges apoptose to connect the lumens of each
Diagram useful

Incorrect fusion causes cleft palate if fusion fails

Underlying cause of congenital abnormalities is usually fusion issues

42
Q

Hypospadias

A

Phallus develops first w no tubes
Remains this way in female
In males tube has to be transported along
Base of penis undergoes invagination - forms trench (orthogonal?)
Forms like an upside down neural tube
Then basically zips up until it reaches end

Can stop early before end causing abnormality

43
Q

Tube branching methods

A

Confluence

Clefting

Sprouting

Intussiception

Many organs dominated by branching epithelia (lung alveolae, mammary gland alveolae, pancreas, kidney nephrons)

44
Q

Confluence

A

Tubes come together and join to make branched structures
(Kind of reverse way ig)

45
Q

Clefting

A

End of one branch swells up
Is held back in places (commonly by ECM) swells around thes held back bits to form branches

46
Q

Sprouting

A

Tube development
Two tubes sprout out the end of one

47
Q

Intussiception basic

A

Way of splitting tube that is carrying something (blood eg)
Blood transport and heart beating needed throughout development
Vascularisation also occurs in adults too
Can’t turn of the blood system to make new vessels so have to do it without interrupting blood flow

48
Q

Branching tip qualities

A

Typically have wedge shape cells going around curve
Lots of actin/myosin making this shape
Cells stick to each other
Push out lamellipodia and filopodia in front of them for navigation

If two lamellipodia in different directions are both gripping equally as well then likely tube will branch oit

49
Q

Mammary gland branched tubes

A

In mouse mammary gland
Flat compared to humans
Long spindly milk ducts form tree
Alveolae at ends of tree that make milk

Ducts form
Branch off and form alveolae

If given HGF (heoatocyte growth factor) - makes branched out dictating tree with not really alveolae
If given neuregukin then will only develop alveolae

Cell development dependent on factors

50
Q

Intussiception process

A

Artery
Capillary bed connects it through tissue
Then to venal system
To add to these need to do so without disrupting blood flow

New capillary formation:
In capillary
Ingrowth of wall forms pillar within tube
Blood can still flow either side
Pillar extends and widens - then that space can be invaded by tissue cells
At this point a hole is made and at no point is blood flow stopped

Now have branch where there was once just one capillary

51
Q

Oriented mitosis

A

Either within the plane of the epithelium- expands the epithelium

Or can be perpendicular to the epithelial plane - pushes one cell out of the epithelium (one daughter stays in epithelium while other is pushed)
Or can thicken the epithelium (eg endometrial thickening in rat)

52
Q

Elective cell death

A

Eg digit separation in hands
Webs between them in early development die off to separate them
-advantageous for some animals to keep webs so this happens less in them or not at sll

Eg internal reproductive systems - potential for male or female
-male secrete anti-mullerian hormones - causes tissues to apoptose - gone in adult

Other way rind in females - some develooong tissues in reproductive system need testosterone presence to not apoptose

53
Q

Signalling for apoptosis in digit webs

A

Gremlin is a BMP antagonist
Expressed in webs of duck but not checke

Put gremlin in chicken - webbing remains there

DB3 (11 decks)

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