Abstract
Glial phagocytosis of superfluous neurons and damaged or aberrant neuronal material is crucial for normal development and maintenance of the CNS. However, the molecular mechanisms underlying the relationship between neuronal death and glial phagocytosis are poorly understood. We describe a novel mechanism that is able to synchronize neuronal cell death and glial phagocytosis of dying neurons in the Drosophila embryonic CNS. This mechanism involves c-Jun N-terminal kinase (JNK) signaling, which is required for developmental apoptosis of specific neurons during embryogenesis. We demonstrate that the dJNK pathway gain-of-function in neurons leads to dJNK signaling in glia, which results in upregulation of glial phagocytosis. Importantly, this promotion of phagocytosis is not mediated by upregulation of the glial phagocytic receptors SIMU and DRPR, but by increasing glial capacity to degrade apoptotic particles inside phagosomes. The proposed mechanism may be important for removal of damaged neurons in the developing and mature CNS.
Highlights
Six Microns Under (SIMU) and Draper (DRPR), which does not depend on apoptosis.[13,14,15] it is not clear how embryonic glia perform when neural damage occurs
The Drosophila c-Jun N-terminal kinase (dJNK) pathway is active in the embryonic central nervous system (CNS) in specific neurons and is involved in developmental neuronal apoptosis
To test the role of dJNK signaling in neuronal apoptosis, we knocked down BSK function by expressing its dominantnegative (DN) form, bskDN, in neurons using the elavGal[4] driver
Summary
Six Microns Under (SIMU) and Draper (DRPR), which does not depend on apoptosis.[13,14,15] it is not clear how embryonic glia perform when neural damage occurs. We show that the dJNK pathway is able to connect between neuronal death and upregulation of glial phagocytosis during Drosophila embryogenesis. Gain-of-function of dJNK signaling in embryonic neurons induces dJNK pathway activation in glia, which promotes glial phagocytosis of apoptotic cells. This upregulation of phagocytosis is not accompanied by increased expression levels of the glial phagocytic receptors SIMU and DRPR or elevated engulfment ability of phagocytic glia, but it promotes degradation of engulfed apoptotic particles. Our work recognizes dJNK signaling as a possible mechanism of upregulation of glial phagocytosis through enhancement of glial capacity to degrade apoptotic particles
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