Common cues regulate neural and vascular patterning

Abstract

Nerves and blood vessels often follow parallel trajectories as they course through the body to their distal targets. Proteins that regulate the process of axon guidance have likewise been shown to play a crucial role in blood vessel migration. With the recent description of the endothelial tip cell as an analog of the axonal growth cone, the nerve-vessel analogy seems complete. Notwithstanding these considerable similarities, one crucial difference remains between neural and vascular guidance. While a navigating axon is but a single cell, a sprouting vessel is composed of multiple cells that must be co-ordinately regulated. Recent studies of the Dll4-Notch1 signaling pathway have provided valuable insight into how the vasculature accomplishes this crucial task.

Figure 1

DLL4-Notch1 signaling enforces the stalk cell phenotype. In the developing murine retina, activation of VEGFR2 by VEGF-A initiates expression of DLL4 in the tip cell. As DLL4 is membrane restricted, juxtracrine signaling between DLL4 and Notch1 on an adjacent cell leads to induction of gene expression programs that enforce the stalk cell phenotype. The consequence is precise control of the number of tip cells at the sprouting front of the vascular plexus.