During the development of peripheral ganglia, 50% of the neurons that are generated undergo apoptosis. How the massive numbers of corpses are removed is unknown. We found that satellite glial cell precursors are the primary phagocytic cells for apoptotic corpse removal in developing mouse dorsal root ganglia (DRG). Confocal and electron microscopic analysis revealed that glial precursors, rather than macrophages, were responsible for clearing most of the dead DRG neurons. Moreover, we identified Jedi-1, an engulfment receptor, and MEGF10, a purported engulfment receptor, as homologs of the invertebrate engulfment receptors Draper and CED-1 expressed in the glial precursor cells. Expression of Jedi-1 or MEGF10 in fibroblasts facilitated binding to dead neurons, and knocking down either protein in glial cells or overexpressing truncated forms lacking the intracellular domain inhibited engulfment of apoptotic neurons. Together, these results suggest a cellular and molecular mechanism by which neuronal corpses are culled during DRG development.
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The authors thank the Statistics and Methodology Services at the Vanderbilt Kennedy Center for assistance on statistical analysis and C. Yoon, C. Jones and other members of the Carter laboratory for technical assistance and helpful suggestions. This work was supported by grants from the US National Institutes of Health (NS048249 and NS064278 to B.D.C., GM067848 to Z.Z.), a Muscular Dystrophy Association Development grant (MDA4023) to H.-H.W., a US National Institutes of Health Minority Access to Research Careers Predoctoral Fellowship (GM079911) to V.V., and the Ministerio de Ciencia e Innovación (SAF), Ministerio de Sanidad (TerCel and Ciberned), Fundación la Caixa, and Generalitat Valenciana (Prometeo) to I.F.
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Wu, HH., Bellmunt, E., Scheib, J. et al. Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor. Nat Neurosci 12, 1534–1541 (2009). https://doi.org/10.1038/nn.2446
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