Maintenance of Glia in the Optic Lamina Is Mediated by EGFR Signaling by Photoreceptors in Adult Drosophila

The late onset of neurodegeneration in humans indicates that the survival and function of cells in the nervous system must be maintained throughout adulthood. In the optic lamina of the adult Drosophila, the photoreceptor axons are surrounded by multiple types of glia. We demonstrated that the adult photoreceptors actively contribute to glia maintenance in their target field within the optic lamina. This effect is dependent on the epidermal growth factor receptor (EGFR) ligands produced by the R1-6 photoreceptors and transported to the optic lamina to act on EGFR in the lamina glia. EGFR signaling is necessary and sufficient to act in a cell-autonomous manner in the lamina glia. Our results suggest that EGFR signaling is required for the trafficking of the autophagosome/endosome to the lysosome. The loss of EGFR signaling results in cell degeneration most likely because of the accumulation of autophagosomes. Our findings provide in vivo evidence for the role of adult neurons in the maintenance of glia and a novel role for EGFR signaling in the autophagic flux.

人类迟发性神经退行性变（neurodegeneration）的特征表明，神经系统细胞的存活与功能必须在整个成年期得到维持。在成年果蝇（Drosophila）的视神经板(optic lamina)中，感光神经元轴突被多种类型的神经胶质细胞（glia）所包裹。本研究证实，成年感光神经元可主动参与其视神经板靶区域内的神经胶质细胞维持过程。该效应依赖于R1-6型感光神经元产生并转运至视神经板、进而作用于视神经板胶质细胞上表皮生长因子受体（EGFR）的配体。表皮生长因子受体信号通路可在视神经板胶质细胞中以细胞自主性方式行使功能，且该功能既是必需的也是充分的。本研究结果显示，表皮生长因子受体信号通路是自噬体/内体（autophagosome/endosome）转运至溶酶体（lysosome）所必需的。表皮生长因子受体信号通路缺失会导致细胞退行性变，这大概率是由自噬体的异常蓄积所引起的。本研究结果为成年神经元维持神经胶质细胞的功能提供了体内实验证据，同时也揭示了表皮生长因子受体信号通路在自噬流（autophagic flux）中的全新作用。