Normal embryonic development is accompanied by elimination of unwanted or aberrant cells through apoptosis and subsequent phagocytosis of apoptotic cells. “Professional” phagocytes, macrophages and immature dendritic cells, and “non-professional” tissue-resident neighboring cells accurately and efficiently remove apoptotic cells during development. Apoptotic cell clearance is a highly dynamic process, which proceeds in four main steps: (1) recruitment of phagocytes to apoptotic cells, (2) recognition, (3) engulfment and (4) degradation of apoptotic cells inside phagocytes. However, very few studies in the field come from live in vivo observations of the process leaving many questions open including time courses of different stages in phagocytosis and comparison between “professional” and “non-professional” phagocytes.
In our research, we use the live Drosophila embryo as a model to elucidate the molecular basis and cell biology of apoptotic cell clearance during development. Two types of phagocytes are studied in parallel: “non-professional” glia in the developing central nervous system (CNS) and “professional” macrophages outside the CNS. By monitoring the embryos with Zeiss LSM 700 confocal microscope and Imaris (Bitplane) software, we demonstrate that tissue-resident clearance by neighboring glia plays a major role in the removal of apoptotic neurons during embryonic CNS development. A detailed investigation of two phagocytic receptors Six-Microns-Under (SIMU) and Draper reveals that SIMU is required for recognition and engulfment of apoptotic cells, whereas Draper is mostly involved in degradation of apoptotic cells by glia and macrophages. Moreover, we aim at understanding how phagocytes acquire their phagocytic ability during development. Our results show that distinct developmental programs are responsible for establishment of embryonic glia and macrophages as potent phagocytes of apoptotic particles.
Since phagocytosis of apoptotic cells is highly conserved throughout animal evolution, investigating its mechanisms in the Drosophila model, which permits comprehensive and dynamic in vivo studies, shall provide new insights into this process with prospective translation into studies in higher organisms.
