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

被引:139
作者
Wu, Hsiao-Huei [1 ,2 ]
Bellmunt, Elena [3 ,4 ]
Scheib, Jami L. [1 ,2 ]
Venegas, Victor [5 ]
Burkert, Cornelia [1 ,2 ]
Reichardt, Louis F. [6 ]
Zhou, Zheng [5 ]
Farinas, Isabel [3 ,4 ]
Carter, Bruce D. [1 ,2 ]
机构
[1] Vanderbilt Univ, Sch Med, Ctr Mol Neurosci, Kennedy Ctr Human Dev, Nashville, TN 37212 USA
[2] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA
[3] Univ Valencia, Dept Biol Celular, E-46100 Burjassot, Spain
[4] Univ Valencia, CIBERNED, E-46100 Burjassot, Spain
[5] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA
[6] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA
基金
美国国家卫生研究院;
关键词
APOPTOTIC CELL ENGULFMENT; IMMUNOHISTOCHEMICAL LOCALIZATION; NERVOUS-SYSTEM; PHAGOCYTOSIS; DRAPER; DEATH; DEGENERATION; DIFFERENTIATION; NEUROGENESIS; MACROPHAGES;
D O I
10.1038/nn.2446
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1534 / U79
页数:10
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