Nerve Cell Signposts in the Blood Vessel Roadmap

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See related article, pages 480–489 The vasculature and the nervous system both form extensively branched networks in the vertebrate body, incorporate into very different tissue environments, and establish connections over long distances. Although there are many obvious morphological and functional differences between blood vessels and nerve fibers, one should not ignore striking conceptual similarities in the assembly of these networks through guided growth and branching processes. There is accumulating evidence that this resemblance is not just coincidental and instead reflects that the morphogenesis of both systems use similar mechanistic principles and molecular tool kits.1–3 During development of the nervous system, neurons extend a long axonal process that carries a highly motile sensory structure, termed growth cone, at its distal tip. Growth cones dynamically form filopodial extensions to explore the spatial environment and recognize repulsive or attractive guidance cues acting as molecular signposts. Growth cones have the ability to interpret a multitude of these signals and decide whether it is appropriate to carry on, stall, retract, or change direction. A series of correct decisions will direct the growing axon to its proper target where it forms synaptic connections. Unlike neurons, endothelial cells do not extend long processes and instead line the inner surface of blood vessels with their cell bodies. During growth and remodeling processes, a specialized endothelial cell, termed tip cell, covers the distal end of vascular sprouts. Tip cells dynamically extend long filopodia and explore signals presented by surrounding cells and the matrix environment.4 Live imaging data obtained in zebrafish embryos and phenotypes of mutant mice indicate that tip cells steer the growth of blood vessels into certain directions, control the branching or fusion of vascular sprouts, and thereby ensure that tissues are adequately connected to the blood circulation. Thus, the role of endothelial tip cells …