[
Bioessays,
2020]
Axon regeneration is a conserved process across the animal kingdom. Recent studies using the soil worm Caenorhabditis elegans as a model system revealed that machineries regulating engulfment of dying cells also control axon regeneration and axon debris removal. In this review, the relationships between the engulfment machinery and the biological processes triggered by axon injury and subsequent axon regeneration drawn from divergent views are examined. In one study, it is found that engulfing cells directly promote axon regeneration. In this context, CED-1 (Drosophila Draper/mouse MEGF10), an engulfment protein expressed on the surface of engulfing cells, functions as a receptor for axon debris removal and as an adhesion molecule for axon regeneration. In other studies, it is shown that those engulfment genes, previously known to function within the engulfing cells for cell corpse removal, can have a cell-autonomous "non-engulfing cell" role in axon regeneration. Together, these findings suggest that engulfment genes are repurposed for neuronal regeneration by acting in both engulfing cells and regenerating neurons.
[
Front Immunol,
2017]
For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin -PS3/-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.