Download Blood Vessels and Nerves

Blood Vessels and Nerves
Common Signals, Pathways and Diseases
Neural and Vascular Cell Fate
Neural and vascular cell fate
In the neural tube (NT), LATERAL INHIBITION through Notch signalling
maintains neuroectodermal stem cell (NSC) potential, and low Notch allows
neuronal cell differentiation. Gradients of sonic hedgehog (Shh), which is
produced by the notochord (N), and bone morphogenetic protein (BMP)
determine the ventral and dorsal identity of neural progenitorsand induce
distinct neuronal cell subtypes in a dose-dependent fashion along the
MORPHOGEN gradient, which explains why distinct types of neuron arise
at different locations — for example, MOTOR NEURONS arise more
ventrally than interneurons in the spinal cord. Notochord-derived Shh
induces somites to release vascular endothelial growth factor (VEGF), which
— through Notch signalling — induces arterial endothelial cell (EC) fate at
the expense of venous EC fate.
Neural stem cells at the vascular niche
Neural stem cells at the vascular niche
Neuroectodermal stem cells (NSCs) at the subventricular zone
(SVZ) lie in the vicinity of the EPENDYMAL CELL layer, which
produces vascular endothelial growth factor (VEGF), at a
vascular niche of numerous capillaries. A shortage of oxygen
during physical exercise or stroke upregulates VEGF levels,
which stimulate both NSCs and capillaries to grow, and
enhance neuronal differentiation, axon outgrowth and neuron
survival. The favourable effect of endothelial cells on
neurogenesis is, at least in part, mediated by the release of
brain-derived neurotrophic factor (BDNF). BV, blood vessel.
Role of Ephrin/Eph interactions in neural crest migration
and intersegmental-vessel branching
Role of ephrin/Eph interactions in neural crest
migration and intersegmental-vessel branching
Neural crest cells migrate only into and through the
rostral half of the somite, and avoid the caudal half
because of repulsive EphB/ephrin-B interactions.
Intersegmental vessels (ISVs) branch at regularly spaced
sites and are guided to migrate through the somites, but
are repelled from entry into the somites through repulsive
EphB/ephrin-B signals. Ao, aorta.
A balance of Sema3A and VEGF determines Nrp1 mediated
growth-cone guidance
A balance of Sema3A and VEGF determines Nrp1
mediated growth-cone guidance
The filopodia of both endothelial cells (ECs) and axons
express neuropilin-1 (Nrp1): the semaphorin Sema3A
repels (jagged arrow) the filopodia, whereas vascular
endothelial growth factor VEGF164 attracts the filopodia,
which drives the EC or axon to move in the direction of
the VEGF gradient. The role of VEGF is best
characterized for ECs.
Role of matrix association of VEGF in vessel
branching
Role of matrix association of VEGF in vessel
branching
Long-range vascular endothelial growth factor (VEGF) gradients allow
endothelial cells (ECs) to maintain their directional course to the target cell,
whereas short-range matrix-bound VEGF guideposts are necessary for ECs
to migrate step-by-step along the journey. a | In the absence of heparinbinding VEGF164 and VEGF188, there is insufficient guidance by shortrange matrix-associated VEGF. The soluble VEGF120 is freely diffusible,
chaotically distributed and fails to provide a directional long-range
guidance cue.As a result, ECs in a single vessel move in all directions, which
leads to vessel expansion rather than directional branching. b | The
VEGF164 isoform provides both short-range matrix guideposts and a longrange gradient of attractant, which allows the vessel to send long sprouts
straight to the target. c | When only matrix bound VEGF188 is present,
there is no long-range attraction, and EC filopodia are misguided over
short distances, often taking wrong turns. ECM, extracellular matrix.
Coordinated patterning of nerves with blood vessels
Coordinated patterning of nerves with blood vessels
a | Artemin (ARTN) is a vessel-derived neurotropic guidance
signal for sympathetic nerve axons; its expression in the
vascular smooth muscle cells (SMCs), from which it is secreted,
gradually shifts distally and thereby guides the sympathetic
nerve fibre to the target organ.
b | Vascular endothelial growth factor (VEGF) is a nervederived arteriotropic guidance signal for small arteries; its
expression in, and secretion from, Schwann cells attracts and
induces arteries, but not veins, to track alongside the nerve
fibres.
Role of VEGF in motor neuron degeneration
Role of VEGF in motor neuron degeneration
a | In the spinal cord, vascular endothelial growth factor
(VEGF) levels must be regulated to maintain adequate
perfusion; however, VEGF is also neurotrophic and stimulates
the survival of motor neurons.
b | Insufficient VEGF levels cause chronic ISCHAEMIA and
deprive motor neurons of essential survival signals, which
results in adult-onset motor neuron degeneration that is
reminiscent of amyotrophic lateral sclerosis (ALS)