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.
Wu
Hsiao-Huei
HH
The Center for Molecular Neuroscience, Kennedy Center For Human Development, and Department of Biochemistry, Vanderbilt University Medical School, Nashville, Tennessee, USA.
Bellmunt
Elena
E
Scheib
Jami L
JL
Venegas
Victor
V
Burkert
Cornelia
C
Reichardt
Louis F
LF
Zhou
Zheng
Z
Fariñas
Isabel
I
Carter
Bruce D
BD
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology*; D010587:Phagocytosis / Q000502:physiology; D011247:Pregnancy; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
C522125:Jedi protein, mouse; C525222:Megf10 protein, mouse; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor