Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

Won-Suk Chung (), Laura E. Clarke, Gordon X. Wang, Benjamin K. Stafford, Alexander Sher, Chandrani Chakraborty, Julia Joung, Lynette C. Foo, Andrew Thompson, Chinfei Chen, Stephen J. Smith and Ben A. Barres
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Won-Suk Chung: Stanford University, School of Medicine
Laura E. Clarke: Stanford University, School of Medicine
Gordon X. Wang: Stanford University, School of Medicine
Benjamin K. Stafford: University of Michigan
Alexander Sher: University of California
Chandrani Chakraborty: Stanford University, School of Medicine
Julia Joung: Stanford University, School of Medicine
Lynette C. Foo: Institute of Molecular and Cell Biology, A *Star, 61 Biopolis Drive, Proteos Building, 138673 Singapore
Andrew Thompson: Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, CLS12250, Boston, Massachusetts 02115, USA
Chinfei Chen: Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, CLS12250, Boston, Massachusetts 02115, USA
Stephen J. Smith: Stanford University, School of Medicine
Ben A. Barres: Stanford University, School of Medicine

Nature, 2013, vol. 504, issue 7480, 394-400

Abstract: Abstract To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes.

Date: 2013
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DOI: 10.1038/nature12776

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