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Advanced developmental biology > Lecture 8 - blood vesssels > Flashcards

Lecture 8 - blood vesssels Flashcards

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1
Q

what cells are the building blocks of all new vessels

A

endothelial

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2
Q

what are differneces in structure between arteries and veins

A

artieres have thick fibrous/elastic layers
veinds thinner fibrous/elastic layers
have valves

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3
Q

what is the first phase of de novo vessel fomration

A

vasculogenesis

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4
Q

what does vasculogenesis involve

A

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

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5
Q

where are angioblasts derived from

A

lateral plate mesoderm

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6
Q

when does vasculogensis occur

A

early in devleopment

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7
Q

when does the specification for artery or wein of angioblast cells occur

A

v early in embryo

when extra embryonic tissue

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8
Q

how is the primary plexus shaped

A

blood flow through = shear stress

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9
Q

what is angiogensis and whats its main role

A

the sprouting of new vessels from pre-existing

creates most of the mature vascular network

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10
Q

describe differences between angiogen and vasculogen

A

angiogensis important in shaping lymph vessels

is reactivated in disease or tissue regen

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11
Q

describe the process of angiogenesis

A

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

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12
Q

what is anastamosis

A

vessels connecting

on contact with extra cellular tip cells lose motile ptype generate EC-EC junction and fuse with recipient vessels

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13
Q

what are pericytes

A

cells that wrap around endothelial cells and supress their poliferation and release cell survival factors inc VEGF/ANG1

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14
Q

what model organism utilised to study blood vessel dev

A

zebrafish - transparent embryo

can inject fluorescent and have live visualisation

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15
Q

what signal is the master regulator of vessel development

A

VEGF

ko - no formation

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16
Q

what vegfr promote angiogensis

A

VEGFR2
VEGFR3
VEGFR2/3 heterodimer

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17
Q

how are vegf act

A

are receptor tyrosine kinases
vegf bind
dimerise / phosphy -act

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18
Q

what vegfr block angiogensis

A

VEGFR1

sVfGFR1

19
Q

what vegf released singal are master regulators of angiogenesis and what rec do they bind to

A 
VEGFA = binds to VEGFR2 and VEGFR1 and sVfGFR1
VEGFC = bind VEGFR2/2-3/3
20
Q

how does VEGFR1 block angiogensis and hence called a decoy

A

has a higher effinity for VEGFA than VEGFR2 but minimal rtk activity = block VEGFA mediated angiogenic signalling

21
Q

how si the spatial control of tip and stalk cells regulated by VEGF and notch

A

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

22
Q

how does differnetial notch expression in the tip and stalk cells give differnet identity

A

activated notch - induced expr of VEGFR1downreg expr VEGFR2 - less responsive to VEGF
- tip cells take lead

23
Q

what are some funcitonal differneces between tip cells and stak cells

A 
tip = extend the filopida /motile/lead new sprouts/guide migration
stalk = non motile/trail tip cells/lumen morphogenses/maintain junctions/connect to parent vessel
24
Q

what occurs if block notch in vessels

A

hypersprouting - all think are tip cell - more motile etc

25
Q

what results when there is an imbalance in angiogensis

A

many disease states
eg paracrine - vegf rel from tumour - incr branch results in abnormal vessels
(norm autocrine rel from endo cells - maintains vascular homeostasis)

26
Q

what drives the migration of tip cells

A

filopodia

27
Q

what oathways guide the tip cell migration

A

Slit/robo
netrin/unc5b
sema[horin /plexin

28
Q

what pathways guide tip cell migration through repulsion

A

Netrin and unc5b
sema3 and plexind1
slit-ROBO

29
Q

describe the importance of plexind1 and the experiments that showed this

A

required for intersegmental patterning in the zebrafish

knockdown with morpholino = no regulation in the migration

30
Q

what pathways guide migration of tip cell through attractin

A

VEGF-Neuropilin

31
Q

what signalling regulates endothelial cell guidance

A

Sena3a2-plxnD1

32
Q

how does plexind1 regulate vegfr

A

blocks vegfr signalling via sVEGFR1

33
Q

what signalling important in specification of arteries and veins

A

notch

34
Q

what fate does a high level of notch activty result in

A

arterial

35
Q

how does hgih notch result in arterial fate

A

expr Hey2 - expr EphrinB2

ligand

36
Q

what notch signalling in venous cells

A

CoupTFIII expression

37
Q

what is ptype if ko notch

A

no arteray vs venous hierarchy

38
Q

what the ptype of ephrinb2 mice

A

look similar to ko notch

39
Q

what is is expressed in venous cells

A

ephb4

the receptor for ephrin b2

40
Q

what is ephrin b2

A

a guidance molecule

ligand

41
Q

what roel does ephrin-eph singalling normally have

A

repulsive

bidirectional

42
Q

what is the result of differential expression of ephrinb2 and ephb4 in A and v

A

v few places where connect

two distinct vessels form

43
Q

what is the ptype with ectopic notch signalling

A

arteriovenous malformations - mess up the intitial segregation

44
Q

describe the signal and changes that occur when quiescent vessel recieves an angiogensis signal

A

mmps act on pericytes -detach from mbn
endo cells loosen junctions
incr permeability of endo cells by vegf allows plasma pr to lay down ecm scaffold
integrin signalling - endo cells move more towards ecm surface

Advanced developmental biology (18 decks)

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