Artery-vein specification in the zebrafish trunk is pre-patterned by heterogeneous Notch activity and balanced by flow-mediated fine-tuning.

Ilse Geudens,Baptiste Coxam,Holger Gerhardt,Andre Rosa,Silvanus Alt,Véronique Gebala,Katja Meier,Anne-Clémence Vion

doi:10.1242/dev.181024

Abstract

ABSTRACTHow developing vascular networks acquire the right balance of arteries, veins and lymphatic vessels to efficiently supply and drain tissues is poorly understood. In zebrafish embryos, the robust and regular 50:50 global balance of intersegmental veins and arteries that form along the trunk prompts the intriguing question of how does the organism keep ‘count’? Previous studies have suggested that the ultimate fate of an intersegmental vessel (ISV) is determined by the identity of the approaching secondary sprout emerging from the posterior cardinal vein. Here, we show that the formation of a balanced trunk vasculature involves an early heterogeneity in endothelial cell behaviour and Notch signalling activity in the seemingly identical primary ISVs that is independent of secondary sprouting and flow. We show that Notch signalling mediates the local patterning of ISVs, and an adaptive flow-mediated mechanism subsequently fine-tunes the global balance of arteries and veins along the trunk. We propose that this dual mechanism provides the adaptability required to establish a balanced network of arteries, veins and lymphatic vessels.

Highlights

Efficient supply of oxygen and nutrient to tissues and organs is dependent on the formation of a hierarchically branched blood vessel network, comprising feeding arteries, capillaries and draining veins
The trunk vasculature exhibits a global balance of arteries and veins, and local patterns favouring alternating vessel identities The zebrafish trunk vasculature consists of a balanced network of arteries and veins (Fig. 1A) (Bussmann et al, 2010)
Secondary sprouts emerging from the posterior cardinal vein (PCV) commonly establish a connection with primary intersegmental vessel (ISV) regardless of their future identity Previous studies identified an early patterning event that occurs in the PCV, establishing either venous or lymphatic cell fate in cells forming the secondary sprouts (Koltowska et al, 2015; Nicenboim et al, 2015)

Summary

Introduction

Efficient supply of oxygen and nutrient to tissues and organs is dependent on the formation of a hierarchically branched blood vessel network, comprising feeding arteries, capillaries and draining veins. The complexity of these differentiation processes and the multitude of chemical and physical morphogenic cues applied to the network appear to provide a daunting task for patterning (Nolan et al, 2013). The fact that many genes are differentially regulated by shear stress in ECs following exposure to blood flow suggests that genetic regulation and flow-dependent mechanisms are not necessarily exclusive, but integrated (Lehoux and Tedgui, 2003; Wragg et al, 2014). How this is achieved and coordinates the correct number, branching pattern and spacing of arteries and veins remains largely unknown

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