Wu Hsiao-Huei, Bellmunt Elena, Scheib Jami L, Venegas Victor, Burkert Cornelia, Reichardt Louis F, Zhou Zheng, Fariñas Isabel, Carter Bruce D
The Center for Molecular Neuroscience, Kennedy Center For Human Development, and Department of Biochemistry, Vanderbilt University Medical School, Nashville, Tennessee, USA.
Nat Neurosci. 2009 Dec;12(12):1534-41. doi: 10.1038/nn.2446. Epub 2009 Nov 15.
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.
在周围神经节发育过程中，所产生的神经元中有50%会发生凋亡。大量凋亡细胞尸体是如何被清除的尚不清楚。我们发现，卫星神经胶质细胞前体是发育中小鼠背根神经节（DRG）中清除凋亡细胞尸体的主要吞噬细胞。共聚焦显微镜和电子显微镜分析显示，清除大部分死亡DRG神经元的是神经胶质前体，而非巨噬细胞。此外，我们鉴定出Jedi-1（一种吞噬受体）和MEGF10（一种所谓的吞噬受体）是在神经胶质前体细胞中表达的无脊椎动物吞噬受体Draper和CED-1的同源物。Jedi-1或MEGF10在成纤维细胞中的表达促进了与死亡神经元的结合，而在神经胶质细胞中敲低这两种蛋白中的任何一种，或过表达缺乏细胞内结构域的截短形式，均会抑制对凋亡神经元的吞噬。这些结果共同揭示了一种在DRG发育过程中清除神经元尸体的细胞和分子机制。
