Blood vessels and nerves: common signals, pathways and diseases

Key Points

  • This article presents an overview of the emerging evidence of how neurons and blood vessels share common genetic pathways to acquire their fate, grow, pattern and navigate, and how both the vascular and neural systems are linked.

  • Both neural and vascular progenitors use common genetic pathways to differentiate into specialized cell subtypes, all of which are optimally equipped to perform specific functions.

  • Angiogenesis and neurogenesis (for example, the birth of new neural stem cells) are closely linked and influence one another — this review highlights the molecular signals that are involved.

  • The organization of both the vascular and nervous systems requires mechanisms that determine boundary formation and the segregation of distinct cell populations: both the vascular and neural systems use common signals.

  • Wiring of the nervous and vascular networks involves the sophisticated use of attractant and repellant signals. Remarkably, both systems often use common genetic pathways to achieve this goal.

  • Vessels and nerves often track together — the recent genetic insights into how they do so are reviewed.

  • There are many more neuro-vascular disorders than originally anticipated; a perspective on their genetic basis and possible treatment is discussed.


Both blood vessels and nerves are vital channels to and from tissues. Recent genetic insights show that they have much more in common than was originally anticipated. They use similar signals and principles to differentiate, grow and navigate towards their targets. Moreover, the vascular and nervous systems cross-talk and, when dysregulated, this contributes to medically important diseases. The realization that both systems use common genetic pathways should not only form links between vascular biology and neuroscience, but also promises to accelerate the discovery of new mechanistic insights and therapeutic opportunities.

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Figure 1: Neural and vascular cell fate.
Figure 2: Neural stem cells at the vascular niche.
Figure 3: Role of ephrin/Eph interactions in neural crest migration and intersegmental-vessel branching.
Figure 4: A balance of Sema3A and VEGF determines Nrp1 mediated growth-cone guidance.
Figure 5: Role of matrix association of VEGF in vessel branching.
Figure 6: Coordinated patterning of nerves with blood vessels.
Figure 7: Role of VEGF in motor neuron degeneration.


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Alzheimer disease

amyotrophic lateral sclerosis


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cerebral arteriopathy

Sturge-Weber syndrome















The embryonic ectoderm that develops into the central and peripheral nervous systems.


A nerve cell that contains a cell body from which dendrites and axons extend to adjacent neurons, and receive and transmit electrical and chemical signals, respectively.


A non-neuronal cell in the brain that lacks axons and dendrites. These cells are subdivided into astrocytes (which make contact with neurons and blood vessels), oligodendrocytes and Schwann cells (which form myelin around axons in the central and peripheral nervous system, respectively), ependymal cells (which line the ventricles) and others.


The process by which a neuron that expresses Notch transmits inhibitory signals to adjacent precursors.


A substance that specifies cell identity as a function of its concentration.


A nerve cell that innervates muscle cells.


The cells that line the passageways in the brain, where the special fluid that protects the brain and spinal cord (cerebrospinal fluid) is made and stored.


A type of non-neuronal brain cell that lacks axons and dendrites, which forms axons in the central nervous system.


Mesenchymal cells that are derived from the neural crest.


One of the three germ layers of the early embryo, which consists of the notochord, muscle and blood.


The cells that line the outside of the heart.


Endothelial progenitors that give rise to endothelial cells.


The common ancestor of haematopoietic and endothelial cells.


Vessels that carry blood from the dorsal aorta between somites to the sides of the neural tube.


The process by which morpholino DNA oligomers lower gene expression by inhibiting translation.


A type of non-neuronal brain cell that lacks axons and dendrites, which forms axons in the peripheral nervous system.


A mutation that does not completely eliminate the wild-type function of a gene and therefore causes a less severe phenotype than a loss-of-function (or null) mutation.


(Astrocyte). A star-shaped glial cell that supports the tissues of the central nervous system.


Any neuronal process (axon or dendrite). This term is typically used to refer to the processes of neurons in cell culture.


Segments of the embryonic hindbrain, which is also known as the rhombencephalon.


The anterior portion of the forebrain, which is also known as the cerebrum, the outer layer of which contains the cortex.


The same side.


The commissures are fibre tracts that connect the two brain hemispheres.


The dorsal part, or roof, of the midbrain.


The aggregation of neuronal processes to form a bundle.


The formation of new blood-vessel branches.


Concerned with the forces that are generated by the heart, and the motion of blood through the cardiovascular system.


A lack of blood supply to an area of the body.


A diminished blood supply to the tissues.


Branching out.


A purple-red mark on the skin that is caused by an excess of blood vessels.


A division or segment of the body.

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Carmeliet, P. Blood vessels and nerves: common signals, pathways and diseases. Nat Rev Genet 4, 710–720 (2003).

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