Review Neural guidance molecules, tip cells, and mechanical factors in vascular development

The vascular system is generated and maintained by reactions of blood vessels to stimuli of several types. The basic outline of the vascular system is determined during development by genetic program-ming, guided by the unique temporal and spatial patterns of structural and molecular features available in the embryo. With establishment of blood flow, control of vascular development is increasingly taken over by feedback signals derived from vascular function, including blood flow and pressure, in addition to those derived from the metabolic state of the tissue. Mechanical and molecular signals also govern the post-natal structural adaptation of vascular beds in response to functional requirements, both during normal, physiological conditions (growth, exercise) and during pathophysiological conditions including ischaemic diseases and tumour growth. The orderly structure of vascular beds emerges as each vessel segment reacts to the local conditions and stimuli that it experiences, according to a common set of genetically determined responses. In this process of angioadaptation, the properties and architecture of vascular beds are determined by the continuous interplay between vascular and cellular reactions to haemodynamic and molecular signals and the functional implications of these reac-tions, constituting a complex feedback system. Here, studies on vascular development and adaptation in response to haemodynamic and molecular factors are integrated, with emphasis on arterial-venou