Lecture 8 - blood vesssels Flashcards
what cells are the building blocks of all new vessels
endothelial
what are differneces in structure between arteries and veins
artieres have thick fibrous/elastic layers
veinds thinner fibrous/elastic layers
have valves
what is the first phase of de novo vessel fomration
vasculogenesis
what does vasculogenesis involve
the differentiation and coalescence of endo progenitors called angioblasts
forming a primitive embryonic plexus
there are two centre of vasculogenesis
the other centre the a/v segregation = go on to form the dorsal aorta and the cardinal vein
where are angioblasts derived from
lateral plate mesoderm
when does vasculogensis occur
early in devleopment
when does the specification for artery or wein of angioblast cells occur
v early in embryo
when extra embryonic tissue
how is the primary plexus shaped
blood flow through = shear stress
what is angiogensis and whats its main role
the sprouting of new vessels from pre-existing
creates most of the mature vascular network
describe differences between angiogen and vasculogen
angiogensis important in shaping lymph vessels
is reactivated in disease or tissue regen
describe the process of angiogenesis
a) tip cell selection = lateral inh of other tc/bm degradation/loss of pericytes/junctional remodel
b) anastamosis - migratory tip cell (gf imp) have invasive behaviour/ stalk cellsrepression of tc fate/formaiton of lumen - when tip cell meet = fuse
c) vessel maturation - ecm deposited/pericyte recruitment/junction stability
what is anastamosis
vessels connecting
on contact with extra cellular tip cells lose motile ptype generate EC-EC junction and fuse with recipient vessels
what are pericytes
cells that wrap around endothelial cells and supress their poliferation and release cell survival factors inc VEGF/ANG1
what model organism utilised to study blood vessel dev
zebrafish - transparent embryo
can inject fluorescent and have live visualisation
what signal is the master regulator of vessel development
VEGF
ko - no formation
what vegfr promote angiogensis
VEGFR2
VEGFR3
VEGFR2/3 heterodimer
how are vegf act
are receptor tyrosine kinases
vegf bind
dimerise / phosphy -act
what vegfr block angiogensis
VEGFR1
sVfGFR1
what vegf released singal are master regulators of angiogenesis and what rec do they bind to
VEGFA = binds to VEGFR2 and VEGFR1 and sVfGFR1 VEGFC = bind VEGFR2/2-3/3
how does VEGFR1 block angiogensis and hence called a decoy
has a higher effinity for VEGFA than VEGFR2 but minimal rtk activity = block VEGFA mediated angiogenic signalling
how si the spatial control of tip and stalk cells regulated by VEGF and notch
lateral inhibiton = spatial control
tip cell induced by VEGF- highVEGFR singal/low notch
VEGFR induce expr of delta in tip cells
results in activation of notch singal in the stalk cell = low VEGF signal and inhibit VEGFR
how does differnetial notch expression in the tip and stalk cells give differnet identity
activated notch - induced expr of VEGFR1downreg expr VEGFR2 - less responsive to VEGF
- tip cells take lead
what are some funcitonal differneces between tip cells and stak cells
tip = extend the filopida /motile/lead new sprouts/guide migration stalk = non motile/trail tip cells/lumen morphogenses/maintain junctions/connect to parent vessel
what occurs if block notch in vessels
hypersprouting - all think are tip cell - more motile etc
