The mechanisms by which apoptotic neurons in the developing dorsal root ganglia are engulfed

Abstract

During development of the nervous system, approximately 50% of the neurons generated undergo apoptosis as part of a normal pruning process. The neuronal corpses must be efficiently cleared to prevent an immune system response. We demonstrated that satellite glial precursor cells are the main phagocytes in the developing dorsal root ganglia (DRG), and identified a novel engulfment receptor necessary for this engulfment, Jedi-1. Jedi-1 contains immunoreceptor tyrosine based activation motifs (ITAMs) that bind to the tyrosine kinase Syk, which is required for phagocytosis. Jedi-1 also contains an NPXY motif that is required for interaction with the adapter protein GULP, which was also necessary for engulfment. Jedi-1 associates with GULP and recruits clathrin heavy chain (CHC), which promotes actin rearrangement required for engulfment. To determine the role of Jedi-1 in vivo we generated jedi-1 -/- mice. Apoptotic neurons accumulate in the developing DRG of jedi-1 -/- mice, and the mice develop autoimmune disease including the production of autoantibodies and kidney dysfunction. The jedi-1 null mice also exhibit excessive itching which results in skin lesions. Our data suggests that this itch phenotype may be due to activation of satellite glial cells in response to defective clearance of apoptotic neurons.