Fish Scales Dictate the Pattern of Adult Skin Innervation and Vascularization

As animals mature from embryonic to adult stages, the skin grows and acquires specialized appendages, like hairs, feathers, and scales. How cutaneous blood vessels and sensory axons adapt to these dramatic changes is poorly understood. By characterizing skin maturation in zebrafish, we discovered that sensory axons are delivered to the adult epidermis in organized nerves patterned by features in bony scales. These nerves associate with blood vessels and osteoblasts above scales. Osteoblasts create paths in scales that independently guide nerves and blood vessels during both development and regeneration. By preventing scale regeneration and examining mutants lacking scales, we found that scales recruit, organize, and polarize axons and blood vessels to evenly distribute them in the skin. These studies uncover mechanisms for achieving comprehensive innervation and vascularization of the adult skin and suggest that scales coordinate a metamorphosis-like transformation of the skin with sensory axon and vascular remodeling.