It has previously been shown that neurovascular tissue promotes osteogenic tissue development, but the inaccessibility of mammalian bones has made studying reciprocal interactions between osteoblasts and neuro-vasculature challenging. Now, Rosalind Bump, Jeffrey Rasmussen and colleagues investigate the neurovascular-bone relationship in the zebrafish caudal fin. By imaging immunostained tissues, transgenic reporters and mutants, the authors show that dorsal root ganglion (DRG) somatosensory neurons extend their peripheral axons to mirror the position of bony fin rays. Although axons and endothelium both exit through dorsal and ventral gaps in the fin rays, they do not align at the same proximal-distal positions. Instead, DRG axons associate with osteoblasts. By observing the endothelium, neurons and osteoblasts over development, the researchers determine that DRG axons migrate and mature with osteoblasts during a period of endothelial remodelling. VEGF inhibition reveals that the endothelium is dispensable for osteoblast and DRG axon patterning. Similarly, genetic mutants demonstrate that DRG neurons are dispensable for endothelial and osteoblast patterning. Conversely, conditional ablation of osteoblasts shows that, although they are not required for early fin organogenesis, they are necessary for endothelial remodelling and axon innervation. Together, these data demonstrate that osteoblasts pattern axons and endothelium during organogenesis to establish a neurovascular-bone relationship.
