Veins and Arteries Build Hierarchical Branching Patterns Differently: Bottom‐Up versus Top‐Down

Kristy Red‐Horse, Arndt F. Siekmann

DOI: 10.1002/bies.201800198


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A tree‐like hierarchical branching structure is present in many biological systems, such as the kidney, lung, mammary gland, and blood vessels. Most of these organs form through branching morphogenesis, where outward growth results in smaller and smaller branches. However, the blood vasculature is unique in that it exists as two trees (arterial and venous) connected at their tips. Obtaining this organization might therefore require unique developmental mechanisms.

arterial trees often form in reverse order.

initial arterial endothelial cell differentiation occurs outside of arterial vessels. These pre‐artery cells then build trees by following a migratory path from smaller into larger arteries, a process guided by the forces imparted by blood flow. Thus, in comparison to other branched organs, arteries can obtain their structure through inward growth and coalescence.

How hierarchical patterned trees form in diverse tubular organs, such as the kidney, lung, and vasculature, has been of scientific interest for several centuries.

establishment of the vasculature follows unique developmental processes, guided by distinct mechanisms important for obtaining proper hierarchical structure and optimal organ function.

The vasculature consists of two interconnected trees. Schematized drawing of arterial and venous blood vessel trees. Note that the two trees are interconnected at their tips, allowing blood to flow from the arteries to the veins.

Although all hierarchical in nature, arteries in different organs and different organisms exhibit slightly different structures.

Advances in our understanding of how arteries are constructed has revealed that arterial trees can form in a unique manner with respect to other hierarchically branched structures—via inward growth rather than outward branching morphogenesis

distinct mechanisms can be responsible for the establishment of hierarchically patterned organs.

live imaging,lineage tracing, and single cell transcriptional analyses indicate that the processes of sprouting, cell fate reacquisition, and cell migration are heavily inter-twined, and are revealing general and organ-specific mechanisms.

it might be necessary to target EC proliferation and migration in ways that were previously not appreciated when enhancing blood flow as a therapeutic aim to diseased or regenerating tissue; and that manipulating these parameters within ECs must be done with caution, because they might affect the formation of venous and arterial trees in opposite ways. Furthermore, it is now clear that genetic and hemodynamic factors interact during artery formation. However, it still needs to be determined exactly how these behaviors result in the exquisitely defined hierarchical branching of the final structure of mature arteries. These new insights are sure to be the subject of exciting studies in the near future.