The engulfment receptor Draper is required for epidermal dendrite ensheathment

Abstract

Our experience of the external world is shaped by somatosensory neurons (SSNs) that innervate our skin and mediate responses to a range of environmental stimuli. The precise innervation patterns and response properties of SSNs are determined in part by specialized interactions with resident skin cells. One such interaction involves the preferential ensheathment of some SSNs by epidermal cells, an evolutionarily conserved intercellular interaction that regulates SSN morphogenesis and mechanical nociceptive sensitivity in Drosophila. The morphogenetic events during ensheathment resemble phagocytic engulfment, therefore we hypothesized that phagocytic receptors mediate molecular recognition of neurites to induce ensheathment. From a screen of epidermally expressed phagocytic receptors we found that the nimrod receptor gene Draper (Drpr) functions in epidermal cells to promote ensheathment. Endogenous Drpr accumulates at sites of epidermal ensheathment but not at epidermal contact sites with unensheathed neurites. Furthermore, overexpressing Drpr increased ensheathment selectively on neurons that are normally ensheathed, suggesting that molecular recognition by Drpr accounts for the specificity of ensheathment. Indeed, we found that an extracellular reporter for the Drpr ligand Phosphatidylserine (PS) accumulates at sites of ensheathment, and that preventing extracellular PS exposure by overexpressing the PS Flippase ATP8a blocked ensheathment. We additionally found that Orion, which encodes a chemokine-like protein that bridges Drpr-PS interactions, is required for sheath formation. Finally, we found that increasing ensheathment by overexpressing Drpr enhanced nociceptor sensitivity to mechanical stimulus. Altogether, these studies show that Drpr acts in epidermal cells to mediate molecular recognition events that drive ensheathment of neurites marked by extracellular PS.