Zygmunt, T., Trzaska, S., Edelstein, L., Walls, J., Rajamani, S., Gale, N., Daroles, L., Ramírez, C., Ulrich, F., and Torres-Vazquez, J. (2012) In parallel interconnectivity of the dorsal longitudinal anastomotic vessels requires both VEGF signaling and circulatory flow. Journal of Cell Science. 125(21):5159-5167.
Blood vessels deliver oxygen, nutrients, hormones and immunity factors throughout the body. To perform these vital functions,
vascular cords branch, lumenize and interconnect. Yet, little is known about the cellular, molecular and physiological mechanisms
that control how circulatory networks form and interconnect. Specifically, how circulatory networks merge by interconnecting
in parallel along their boundaries remains unexplored. To examine this process we studied the formation and functional maturation of
the plexus that forms between the Dorsal Longitudinal Anastomotic Vessels (DLAVs) in the zebrafish. We find that the migration
and proliferation of endothelial cells within the DLAVs and their Segmental (Se) vessel precursors drives DLAV plexus formation.
Remarkably, the presence of Se vessels containing only endothelial cells of the arterial lineage is sufficient for DLAV plexus
morphogenesis, suggesting that endothelial cells from the venous lineage make a dispensable or null contribution to this process.
The discovery of a circuit that integrates the inputs of circulatory flow and Vascular Endothelial Growth Factor (VEGF) signaling
to modulate aortic arch angiogenesis, together with the expression of components of this circuit in the trunk vasculature,
prompted us to interrogate the role of these inputs and their relationship during DLAV plexus formation. We find that circulatory
flow and VEGF signaling make additive contributions to DLAV plexus morphogenesis, rather than acting as essential inputs with
equivalent contributions as they do during aortic arch angiogenesis. Our observations underscore the existence of context-dependent
differences in the integration of physiological stimuli and signaling cascades during vascular development.