A conserved morphogenetic mechanism for epidermal ensheathment of nociceptive sensory neurites

Humans and other animals perceive and interact with the outside world through their sensory nervous system. Nerve cells, acting as the body’s ‘telegraph wires’, convey signals from sensory organs – like the eyes – to the brain, which then processes this information and tells the body how to respond. There are different kinds of sensory nerve cells that carry different types of information, but they all associate closely with the tissues and organs they connect to the brain. Human skin contains sensory nerve cells, which underpin our senses of touch and pain. There is a highly specialized, complex connection between some of these nerve cells and cells in the skin: the skin cells wrap tightly around the nerve cells’ free ends, forming sheath-like structures. This ‘ensheathment’ process happens in a wide range of animals, including those with a backbone, like fish and humans, and those without, like insects. Ensheathment is thought to be important for the skin’s nerve cells to work properly. Yet it remains unclear how or when these connections first appear. Jiang et al. therefore wanted to determine the developmental origins of ensheathment and to find out if these were also similar in animals with and without backbones. Experiments using fruit fly and zebrafish embryos revealed that nerve cells, not skin cells, were responsible for forming and maintaining the sheaths. In embryos where groups of sensory nerve cells were selectively killed – either using a laser or by making the cells produce a toxin – ensheathment did not occur. Further studies, using a variety of microscopy techniques, revealed that the molecular machinery required to stabilize the sheaths was similar in both fish and flies, and therefore likely to be conserved across different groups of animals. Removing sheaths in fly embryos led to nerve cells becoming unstable; the animals were also less sensitive to touch. This confirmed that ensheathment was indeed necessary for sensory nerve cells to work properly. By revealing how ensheathment first emerges, these findings shed new light on how the sensory nervous system develops and how its activity is controlled. In humans, skin cells ensheath the nerve cells responsible for sensing pain. A better understanding of how ensheathments first arise could therefore lead to new avenues for treating chronic pain and related conditions.