L9 - Development of blood and blood vessels

Question 1

where blood and blood vessels come from

Answer 1

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

Question 2

cells that make up the vascular system

Answer 2

1. 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

3. bloody cells
   erythrocytes, lmypocytes, macrophages, platelets for immune sys blood clotting and oxygen transport

Question 3

what determines their fate

Answer 3

haemotopoic stem cells originate from specialised haemogenic endothelial
notch signalling active = haemotopoetic lineage
Wnt pathway active = endothelial lineage

Question 4

endohelial cells origin

Answer 4

early: extraembryonic (yolk sac) and splanchnic mesoderm
later: any mesoderm except prechordal and axial mesoderm

Question 5

yolk sac blood islands

Answer 5

• common origin of blood cells and endothelial cells

Question 6

haemangioblast -

Answer 6

common precusors which give birth to blood or endothelial cells

Question 7

microglia origin

Answer 7

in early embrogenssis

primitive macrophages fform from yolk sac blood islands
colonise neural tube

self maintained population throughout life

Question 8

two phases in development of vasculature

Answer 8

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

Question 9

two phases in development of vasculature

Answer 9

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

Question 10

development of dorsal aorta

Answer 10

initially =
2 aortas that fuse in the midline

dua origin
early = lateral splanchnic mesoderm

later = paraxial mesoderm

Question 11

2 mechanisms of blod vessel formation

Answer 11

1. vasculogenesis
   from mesoderm progenitors
   mesoderms specified into endothelial precursor cells and then assemble into blood vessel
   - extraembryonic region and how dorsal aorta is formed
2. angiogenesis sprouting of existing endothelial cells blood vessels can fuse

Question 12

vascularisation of the CNS

Answer 12

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

Question 13

transcriptional control of endothelial development

Answer 13

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

Question 14

oxygen sensing + vascularisation

Answer 14

hypnoxia prevents proline hydroxylation and degradation of the HIF transcription factor = activation of VEGF expression

tumour inducing angiogenesis = target for cancer therapy

Question 15

mural cells - around blood vessels

Answer 15

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

Question 16

3 basic types of blood vessels + formation

Answer 16

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

Question 17

blood vessel formation in steps

Answer 17

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

Question 18

primitive to definitive haematopoiesis

Answer 18

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

Question 19

stem and progenitor cells

Answer 19

either myeloid or lymphoid lineages

progenitor cels are still proliferating = unipotent i,e, erythrobyepro erythrocytes - restricted fate to make more red blood cells

Question 20

identifying progenitor cells

Answer 20

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

Question 21

haematopoietic stem cell

Answer 21

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

Question 22

cytokine control of haemotopoiesis

Answer 22

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

Question 23

blood and blood vessels have a shared origin - haemangioblast

Answer 23

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