L9 - Development of blood and blood vessels Flashcards
where blood and blood vessels come from
early embryonic stages = outside the embryo primitive hematopoeisis in the embryo sac (amniots) or ventral blood islands (anamniontes)
first blood islands form outside embryo proper
mainly yolk sac and chorion and developing allantois -
haematopoisis in placenta (they will all fuse together)
= primary plexus of blood vessels
organogenesis stage
foetal stages: feotal live
adult = bone marrow
cells that make up the vascular system
- endothelial cells form the arterial, venal and lymphatic walls
polarity with the basal side
basal lamina around the lamina
2, mural cells support vessels
smooth muscle and pericytes
- bloody cells
erythrocytes, lmypocytes, macrophages, platelets for immune sys blood clotting and oxygen transport
what determines their fate
haemotopoic stem cells originate from specialised haemogenic endothelial
notch signalling active = haemotopoetic lineage
Wnt pathway active = endothelial lineage
endohelial cells origin
early: extraembryonic (yolk sac) and splanchnic mesoderm
later: any mesoderm except prechordal and axial mesoderm
yolk sac blood islands
- common origin of blood cells and endothelial cells
haemangioblast -
common precusors which give birth to blood or endothelial cells
microglia origin
in early embrogenssis
primitive macrophages fform from yolk sac blood islands
colonise neural tube
self maintained population throughout life
two phases in development of vasculature
early: extra emryoin
yolk sac blood islands forming primary plesux
then intraembryonic
plexus forms aorta and cardinal vein
then more vesseld then artery and veins and capillary network
two phases in development of vasculature
early: extra emryoin
yolk sac blood islands forming primary plexus
then intraembryonic
plexus forms aorta and cardinal vein
then more vessels then artery and veins and capillary network
major blood vessels in embryo = dorsal aorta + cardinal vein temporarily main site of haematopoiesis
link of embryonic vasculature with yolk sac = vitelline vein and artery
in the mouse: rapid
- dorsal aorta first
then cephalic plexus and intersomitic vessels
development of dorsal aorta
initially =
2 aortas that fuse in the midline
dua origin
early = lateral splanchnic mesoderm
later = paraxial mesoderm
2 mechanisms of blod vessel formation
- vasculogenesis
from mesoderm progenitors
mesoderms specified into endothelial precursor cells and then assemble into blood vessel
- extraembryonic region and how dorsal aorta is formed - angiogenesis sprouting of existing endothelial cells blood vessels can fuse
vascularisation of the CNS
no intrinsic angioblasts in neural tibe = brain vascularure is formed from extrinsic mesodermal endothlial cells
vasculogenesis - perineural vascular plexus
sprouting angiogensis = capillary sprouts
initiated by TIP cells
delta notch signalling
if there is cell the recieved a high level of VEGF will turn into a TIP cell - low notch activity but up regulates notch signalling to neighbouring cells
transcriptional control of endothelial development
top regulator for haematopoietic and endothelial lineage = SCL= Tal1
Etv2 angioblast specification regulator
VEGF signalling for blood vessel formation
expressed by enothelial pregenitor
the receptors are: VEGFR1 VEGFR2
NRP! co recept
VEGF -A is an attractant for angioblasts to the neural tune
induces formation of vascular plexus in presomitic medoderm eplant
oxygen sensing + vascularisation
hypnoxia prevents proline hydroxylation and degradation of the HIF transcription factor = activation of VEGF expression
tumour inducing angiogenesis = target for cancer therapy
mural cells - around blood vessels
PDGF-@ secreted by endothelial tip cells attracts mural cells
angiopoietin 1 ensures vessel integrity and quiescence (non-srouting)
2 causes loss of mural endothelial contacts
with VEGF = allows sprouting w/out VEGF = vascular regression
3 basic types of blood vessels + formation
Arteries = blood from the heart = high pressure
thick outer layers w smooth mule = elsastic fibres
Veins =blood too the heart - low pressure
thinner outer layer s = valves
capillaries - gas exchange + nutrients to tissue
fate of angioblasts - artery vs vein = ntch signalling
High notch = arteries+ ephrin B2
low Notch = veins + Eph84
ephrin B2 and EpB4 bind to each other = mediates fusion of capillary network
blood vessel formation in steps
FGF signalling specifies mesoderm cells + hemangioblast = give rise to endothelial cells and primitive blood cells where VEGF signalling is important
after first blood vessels formed they attract mural cells from persites signalling to endothelial cells
VEGF is a factor for angiogenesis
crosstalk between blood vessels and endothelial cells mural cells PDGF and TGF
specification of arteries and cells with notch signalling + fgf
primitive to definitive haematopoiesis
blood is extra embryonic from yolk of hemangioblast = blood vessels + cells + stem cells
Aorta,gonad + mesonephros
placenta =
fetal liver = cycling long term hemopoetic stem cells
Bone marrow transient population
stem and progenitor cells
either myeloid or lymphoid lineages
progenitor cels are still proliferating = unipotent i,e, erythrobyepro erythrocytes - restricted fate to make more red blood cells
identifying progenitor cells
using colony assays
cells cultured @ low density in high viscosity medium
stel cells will divide + dfferentiate into colony forming unit
cells types in the colony can be identified
haematopoietic stem cell
SCL transcription factor required for haematopoiesis
T-al1 expression is upregulated in large numbers of T-all patients
cross activation of scl, gata2 and fli1 maintains stem cell character in HSC
gata1 = disrupts triad shutting down exp o fgata2 = triggerring differentiation
gat1 thyroid and pu1 reulatedcontrol of cell diferentiation
gata 1 - guides cells to erythroid fate = red blood cells
pu1 myeloid fate = macrophage
cytokine control of haemotopoiesis
combinatorial signalling by a range of sytokines regulate progressve differentiona
adults human haematopoiesis rate perday
175 billion red cells
70 billion neutrophils eosinophils basophils
175 billion platelets
erythropoietin = cytokine
for red blood cells
controlling the proliferation of the erythroid proliferation
epo signals though JAK/STAT pathway
blood and blood vessels have a shared origin - haemangioblast
early vasculogensis - fro endothelium precursor cells and later angiogensis - sprouting from exisiting vessels
VEGF signalling is a factor in endothelial development
arteries + veins are specific early in differntiation
blood cells are derived from haematopoietic stem cells
cytokines and transcription factors regulate differentation into the different cell types
