Mechanisms Of Development Flashcards
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
Animal way of changing cell sheet shape
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
Notochord shape change in Corella inflata (chordate)
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
Convergent extension mechanism
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
Ways of making tubes
Axial invagination
Orthogonal invagination
Evagination
Cavitation
Wrapping
Axial invagination
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
Orthogonal invagination
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
Evagination
Opposite of invagination
Cavitation
Process of fluid filled cavity forming inside the morula (cavity is the bladtocoel)
Forming blastocyst
Wrapping
Cell sheet wraps around to surround a lumen
Changing cell shape
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?
Orthogonal invagination of neural tube
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
The need for fusion of cell sheets
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
3 ways of fusing
Wound healing
Tube connection
Apical sided meet
Wound healing
Edges of sheet move together and fuse
Scar prone - sealed with scar tissue in adults to prioritise barrier function - fetuses prefer scarless healing
Tube connection
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
Apical sides meet
Similar to tube connection
Except that it is the apical sides that meet
Secondary palate formation
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
Hypospadias
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
Tube branching methods
Confluence
Clefting
Sprouting
Intussiception
Many organs dominated by branching epithelia (lung alveolae, mammary gland alveolae, pancreas, kidney nephrons)
Confluence
Tubes come together and join to make branched structures
(Kind of reverse way ig)
Clefting
End of one branch swells up
Is held back in places (commonly by ECM) swells around thes held back bits to form branches
Sprouting
Tube development
Two tubes sprout out the end of one
Intussiception basic
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
Branching tip qualities
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
Mammary gland branched tubes
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
Intussiception process
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
Oriented mitosis
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)
Elective cell death
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
Signalling for apoptosis in digit webs
Gremlin is a BMP antagonist
Expressed in webs of duck but not checke
Put gremlin in chicken - webbing remains there
