Epigenetic Control of Animal Development - Building the Most Complex Structure on Earth - page 159

Primary capillay
plexus formation

(A) (D)

Peripheral nerve-
induced arteriogenesis

E11.5

Axon and
Schwann cell-
derived VEGF-A
induces
arteriogenesis

Sensory axon
innervation

(B)

EphrinB2+/Nrp-1+
artery

E15.5

Sympathetic axon
innervation

Schwann cells

(E)

Nerve/Schwann cell-
derived signals

E13.5

(C)

Nerve-vessel
alignment

Artery surrounded by
smooth muscle cells

Sympathetic axon

Remodeled
blood vessel

E16.5+

E14.5

EC migration

Figure 3.31 Model of blood vessel patterning by peripheral nerves in developing limb
skin. (A) Blood vessels coalesce into a primary capillary plexus and begin to undergo
remodeling by E11.5 before peripheral axon innervation develops in the limb. (B) Sensory
axons and associated Schwann cells innervate the limb by E13.5 and secrete signals to pattern
the primary vascular plexus. (C) In response to nerve and Schwann cell-derived signals,
endothelial cells migrate toward and begin to align with peripheral nerves. (D) Blood vessels
that have aligned with peripheral nerves undergo arteriogenesis in response to nerve and
Schwann cell-derived VEGF-A. Aligned blood vessels upregulate arterial markers such as
ephrinB2 and Nrp-1. Upregulation of Nrp-1 is thought to increase endothelial cell response to
VEGF-A signaling. (E) After sensory nerve-induced arteriogenesis is complete, sympathetic
axons innervate the limb, utilizing the blood vessels and sensory nerves as a template for
migrations. Sympathetic axons invade the arterial smooth muscle layer to regulate local
control of vascular tone.
Source : From James and Mukouyama (2011) .

Mukoyama's model explains the vasculogenetic function of the peripheral nerv-
ous system. Another model is presented to explain the patterning of the perineural
vessel plexus (PNVP) and the intraneural vessel plexus in the neural tube by the neu-
ral tube itself and the formation of the blood-brain barrier ( James and Mukouyama,