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Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor


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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Figure 1: Neuron corpses in developing DRG are engulfed by BFABP-positive SGC precursors.
Figure 2: Electron micrographs of apoptotic bodies engulfed and ingested by SGC precursors in embryonic E12.5 DRGs.
Figure 3: Glial cells engulf dead neurons induced by NGF withdrawal in vitro.
Figure 4: Putative Draper and CED-1 homologs, Jedi-1 and MEGF10, are expressed in developing peripheral glial cells.
Figure 5: The extracellular domain of Jedi-1 recognizes cell corpses when expressed in C. elegans engulfing cells.
Figure 6: Jedi-1 and MEGF10 expressed in HEK293 cells enable binding to dead neurons.
Figure 7: Ectopic expression of Jedi-1 or MEGF10 in glial cells promotes neuronal corpse engulfment.
Figure 8: Neuronal corpse engulfment by glial cells requires endogenous Jedi-1 and MEGF10.


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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.

Author information




H.-H.W. and B.D.C. initiated and developed the overall concept and design of the project. H.-H.W. also performed, analyzed and interpreted most of the experiments and prepared the initial version of the manuscript. E.B. performed the quantitative histological analysis of neuronal corpse engulfment in Ntf3+/+ and Ntf3−/− mice. J.L.S. generated some of the Jedi-1 and MEGF10 constructs, performed the binding experiment and some of the immunostaining analyses. V.V. performed all of the experiments with C. elegans. C.B. assisted with the immunostaining on sections and generated the shRNA construct for MEGF10. L.F.R. provided technical expertise for electron microscopy analysis and critical intellectual input for this study. I.F. performed the electron microscopy analysis, supervised the quantitative histological analysis and provided intellectual input. Z.Z. designed and supervised the C. elegans study and provided intellectual input. B.D.C. directed the overall project and prepared the final version of the manuscript.

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Correspondence to Bruce D Carter.

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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).

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