טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSellman Yael
SubjectMolecular Mechanisms in Regulation of Phagocytic
Receptor Six-Microns-Under (SIMU)
DepartmentDepartment of Medicine
Supervisor Dr. Estee Kurant
Full Thesis textFull thesis text - English Version


Abstract

The elimination of unneeded or damaged cells through programmed cell death, especially apoptosis, plays an essential role in metazoan development and tissue homeostasis. The final stage of this elimination is clearance of apoptotic cells through phagocytosis. Deficiencies in phagocytosis of apoptotic cells can lead to inflammation, autoimmune diseases and tumor progression. Phagocytosis of apoptotic cells is performed by two types of phagocytes: “professional”- macrophages and immature dendritic cells, and “non-professional”- tissue-resident neighboring cells. During Drosophila development, the elimination of superfluous cells through apoptosis and phagocytosis occurs in three main phases: embryogenesis, pupa, and early adult. Much of the cell death occurs in the nervous system, where almost half the cells are removed. Apoptotic cells in Drosophila are cleared by "professional" phagocytes - macrophages and "non-professional" glial cells, which have been shown to act as potent phagocytes in the central nervous system (CNS).Several genes have been implicated in apoptotic cell clearance in Drosophila, including six micron under (simu), which encodes for a non-signaling phagocytic receptor required for efficient apoptotic cell clearance by glia in the nervous system and by macrophages elsewhere. SIMU is expressed solely during stages when developmental apoptosis occurs. In the embryo, SIMU is found exclusively on phagocytic cell membranes, suggesting precise spatial and temporal regulation of its expression. The aims of this work were to elucidate the molecular mechanisms controlling SIMU specific expression during development and tumorigenesis. Our results show that SIMU precise regulation does not depend on apoptosis, though this is part of a developmental program controlling phagocytic function of glia and macrophages, which is critical for proper embryonic development. Specifically, we show that regulators of glial identity gcm and repo control simu transcription in glia and not in macrophages, whereas apoptosis levels do not have any effect on simu expression. These data suggest that glia are well prepared for developmental cell clearance in the CNS independently of apoptosis itself.