Microglia in the developing retina couple phagocytosis with the progression of apoptosis via P2RY12 signaling.
Microglia in the developing retina couple phagocytosis with the progression of apoptosis via P2RY12 signaling.
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DOI：
10.1002/dvdy.163
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发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
Mitchell DM
中科院分区：
文献类型：
--
作者：
Blume ZI;Lambert JM;Lovel AG;Mitchell DM
小胶质细胞定植在发育中的脊椎动物中枢神经系统，与发育性细胞凋亡的检测一致。我们对完整组织中细胞凋亡与小胶质细胞清除垂死细胞的关系的理解主要基于固定样品，鉴于小胶质细胞是高度能动的和移动的吞噬细胞，这是有限的。在这里，我们使用了一个系统的小胶质细胞耗竭和在斑马鱼体内实时成像，以直接解决小胶质细胞吞噬凋亡细胞在正常视网膜发育过程中，吞噬作用的相对时间与凋亡进展，和P2RY12信号转导的贡献，这一过程。小胶质细胞的耗竭导致视网膜中大量凋亡细胞的积累。实时成像揭示了小胶质细胞吞噬的精确时间与凋亡的进展，以及被吞噬的凋亡细胞的动态运动和位移。P2RY12信号传导的抑制延迟了凋亡细胞的小胶质细胞清除。死亡细胞的小胶质细胞吞噬与凋亡进展一致，并且需要P2RY12信号传导，表明小胶质细胞P2RY12信号传导在发育和损伤反应之间共享。我们的工作提供了重要的在体内了解发育中的脊椎动物视网膜的凋亡细胞清除的动态，并提供了一个基础，以了解健康和疾病中的小胶质细胞吞噬行为。
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. 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. 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.
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DOI：
10.1016/s0165-3806(96)00119-8
发表时间：
1996-11-22
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Egensperger, R;Maslim, J;Stone, J
通讯作者：
Stone, J
影响因子：
6.1
作者：
Diaz-Aparicio I;Beccari S;Abiega O;Sierra A
通讯作者：
Sierra A
影响因子：
9.8
作者：
Abiega O;Beccari S;Diaz-Aparicio I;Nadjar A;Layé S;Leyrolle Q;Gómez-Nicola D;Domercq M;Pérez-Samartín A;Sánchez-Zafra V;Paris I;Valero J;Savage JC;Hui CW;Tremblay MÈ;Deudero JJ;Brewster AL;Anderson AE;Zaldumbide L;Galbarriatu L;Marinas A;Vivanco MD;Matute C;Maletic-Savatic M;Encinas JM;Sierra A
通讯作者：
Sierra A
影响因子：
7.3
作者：
Barth ND;Marwick JA;Vendrell M;Rossi AG;Dransfield I
通讯作者：
Dransfield I
影响因子：
4.8
作者：
Brumatti, Gabriela;Sheridan, Clare;Martin, Seamus J.
通讯作者：
Martin, Seamus J.