Mechanisms Of Development Flashcards
(53 cards)
Mammlian cell movement
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
Leading edge autonomy
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
Leading edge tug of war
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
Germline separation
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
Guidance cues for primordial germ cells
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
Kit gradient and skin pigment
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
Melanoma metastasis danger
In melanoma the melanocytes may revert to this migratory state - gigeing metastasis risk
Kit mutations and neural crest migration in mice
Cause unlimbered latched at furthest migration points for these neural crest cells (belly)
Run out of signal strength before reaching it I think
The enteric nervous system
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
Enteric nervous system migration story
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
Signalling mechanism for ENS migration
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
Reasons for for collective cell migration
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
Mutants for ENS migration
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
Issues with missing ENS ganglia
Ganglia control peristalsis
Having missing ones is bad
In colonic aganglionosis-no peristalsis in colon - can get severe constipation - needs surgical intervention
Growth cone basic info
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
EDN3 and GDNF signalling in neural crest settling
EDN3 binds EDNRB TM receptor
Is anti migratory and pro proliferation signalling in cell
Repulsive substrates and growth cones
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
Growth cone collapse induced
Ephrin
Ephrin growth cone repulsion action
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
Collapse induction use in defining paths
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
Collapse inducing Ephrin in sorting retinal axons in binocular vision
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
Collapse inducing Ephrin in sorting retinal axons in more general vision context
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
Epithelia basic
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
Plant method for changing shape tissue shape
Cells stay in same relative positions to each other and cells themselves deform
Common in plants as they don’t have much cell movement
