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

Nat Neurosci. 2009 Dec;12(12):1534-41. doi: 10.1038/nn.2446. Epub 2009 Nov 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cells, Cultured
  • Female
  • Fibroblasts / physiology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology*
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Humans
  • Kidney / cytology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Nerve Growth Factor / pharmacology
  • Neuroglia / cytology*
  • Phagocytosis / physiology
  • Pregnancy
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / drug effects
  • Stem Cells / drug effects
  • Stem Cells / physiology*

Substances

  • Jedi protein, mouse
  • Megf10 protein, mouse
  • Membrane Proteins
  • Green Fluorescent Proteins
  • Nerve Growth Factor