Neuroblast sensory quiescence depends of vascular cytoneme contacts and sensory neuronal differentiation requires initiation of blood flow

Abstract

SummaryIn many organs, stem cell function depends on the communication with their niche partners. Cranial sensory neurons develop in close proximity to blood vessels, however whether vasculature is an integral component of their niches is yet unknown. Here, two separate, novel roles for vasculature in cranial sensory neurogenesis in zebrafish are uncovered. The first involves precise spatiotemporal endothelial-neuroblast cytoneme contacts and Dll4-Notch signalling to restrain neuroblast proliferation. Secondly, we find that blood flow onset triggers a transcriptional response to modify neuroblast metabolic status and is required for sensory neuron differentiation. In contrast, no role of sensory neurogenesis in vascular development is found, suggesting a unidirectional signalling from vasculature to sensory neuroblasts. Altogether, we demonstrate that the cranial vasculature constitutes a hitherto unrecognized niche component of the sensory ganglia that regulates the pace of their growth and differentiation dynamics.Highlights♦ Vasculature is part of the cranial sensory ganglia niche and regulates neurogenesis.♦ Cytoneme contacts between endothelial cells and sensory neuroblasts are required for neuroblast quiescence.♦ Endothelial Dll4 and neuroblast Notch1 signal to regulate the growth of cranial sensory ganglia.♦ Initiation of blood flow triggers a transcriptional metabolic switch and sensory neuronal differentiation.