PUBLICATION
Microglia in the developing retina couple phagocytosis with the progression of apoptosis via P2RY12 signaling
- Authors
- Blume, Z.I., Lambert, J.M., Lovel, A.G., Mitchell, D.M.
- ID
- ZDB-PUB-200221-40
- Date
- 2020
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 249(6): 723-740 (Journal)
- Registered Authors
- Keywords
- Microglia, developmental apoptosis, p2ry12, phagocytosis, retina, zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Apoptosis/physiology
- Metronidazole/pharmacology
- Microglia/cytology*
- Microglia/drug effects
- Microglia/metabolism*
- Phagocytosis/drug effects
- Phagocytosis/physiology
- Receptors, Purinergic P2Y12/genetics
- Receptors, Purinergic P2Y12/metabolism*
- Retina/cytology*
- Retina/drug effects
- Retina/metabolism*
- Signal Transduction/drug effects
- PubMed
- 32072708 Full text @ Dev. Dyn.
Citation
Blume, Z.I., Lambert, J.M., Lovel, A.G., Mitchell, D.M. (2020) Microglia in the developing retina couple phagocytosis with the progression of apoptosis via P2RY12 signaling. Developmental Dynamics : an official publication of the American Association of Anatomists. 249(6):723-740.
Abstract
Background Microglia colonize the developing vertebrate central nervous system coincident with detection of developmental apoptosis. Our understanding of apoptosis in intact tissue in relation to microglial clearance of dying cells is largely based on fixed samples, which is limiting given that microglia are highly motile and mobile phagocytes. Here, we used a system of microglial depletion and in vivo real-time imaging in zebrafish to directly address microglial phagocytosis of apoptotic cells during normal retinal development, the relative timing of phagocytosis in relation to apoptotic progression, and the contribution of P2RY12 signaling to this process.
Results Depletion of microglia resulted in accumulation of numerous apoptotic cells in the retina. Real-time imaging revealed precise timing of microglial engulfment with the progression of apoptosis, and dynamic movement and displacement of engulfed apoptotic cells. Inhibition of P2RY12 signaling delayed microglial clearance of apoptotic cells.
Conclusions Microglial engulfment of dying cells is coincident with apoptotic progression and requires P2RY12 signaling, indicating that microglial P2RY12 signaling is shared between development and injury response. Our work provides important in vivo insight into the dynamics of apoptotic cell clearance in the developing vertebrate retina and provides a basis to understand microglial phagocytic behavior in health and disease. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping