Developmental regulation of glial cell phagocytic function during Drosophila embryogenesis

• We study establishment of embryonic glia as primary phagocytes in the CNS.
• Phagocytic ability of embryonic glia does not depend on apoptosis.
• Glial phagocytosis is determined by expression of receptors SIMU and DRPR.
• GCM directly regulates simu expression in glia while drpr expression requires REPO.
• Glial developmental program regulates phagocytic competence.

The proper removal of superfluous neurons through apoptosis and subsequent phagocytosis is essential for normal development of the central nervous system (CNS). During Drosophila embryogenesis, a large number of apoptotic neurons are efficiently engulfed and degraded by phagocytic glia. Here we demonstrate that glial proficiency to phagocytose relies on expression of phagocytic receptors for apoptotic cells, SIMU and DRPR. Moreover, we reveal that the phagocytic ability of embryonic glia is established as part of a developmental program responsible for glial cell fate determination and is not triggered by apoptosis per se. Explicitly, we provide evidence for a critical role of the major regulators of glial identity, gcm and repo, in controlling glial phagocytic function through regulation of SIMU and DRPR specific expression. Taken together, our study uncovers molecular mechanisms essential for establishment of embryonic glia as primary phagocytes during CNS development.