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We are interested in interactions between the two fundamental cell types of the nervous system, neurons and glia. My laboratory seeks to understand how neuron-glia communication facilitates the formation, elimination and plasticity of synapses—the points of communication between neurons—during both healthy development and disease.
We focus on the role of neuron-glia and neural-immune interactions in the patterning of neural circuits. We and our collaborators have identified an unexpected role for glia and components of the innate immune system in synaptic pruning. We find that astrocytes induce neuronal expression of complement C1q, the initiating protein of the classical complement cascade (which tags unwanted cells and debris for elimination in the immune system). C1q and downstream complement proteins target synapses and are required for synapse elimination in the developing visual system. Importantly, we find that C1q becomes aberrantly upregulated and is relocalized to synapses in the early stages of glaucoma, suggesting that a similar elimination mechanism may be in place during both healthy central-nervous-system (CNS) development and neurodegenerative diseases.
Our ongoing studies are directed toward defining the cellular and molecular mechanisms underlying synapse elimination during health and disease, with emphasis on the role of complement in this process. In addition to our interest in CNS neurodegenerative diseases, we are currently collaborating with other laboratories to further probe the potential link between complement proteins and synapse loss in the pathogenesis of epilepsy and neurodevelopmental disorders.
A microglial cell labeled with green fluorescent protein (GFP). The microglial processes are closely positioned and interacting with retinal ganglion cell inputs (red and turquoise) in the dorsal lateral geniculate nucleus of the thalamus. Image was acquired from a postnatal day 30 mouse.
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论文共 155 篇作者统计合作学者相似作者
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Michael S. Placzek,Daniel K. Wilton,Michel Weïwer, Mariah A. Manter, Sarah E. Reid, Christopher J. Meyer,Arthur J. Campbell,Besnik Bajrami, Antoine Bigot, Sarah Bricault, Agathe Fayet,Arnaud Frouin,
NATURE MEDICINE (2023)
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Michael-John Dolan,Martine Therrien, Saša Jereb,Tushar Kamath,Vahid Gazestani, Trevor Atkeson,Samuel E. Marsh,Aleksandrina Goeva, Neal M. Lojek,Sarah Murphy,Cassandra M. White,Julia Joung,
Nature Immunologyno. 8 (2023): 1-9
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biorxiv(2023)
Lasse Dissing-Olesen,Alec J. Walker,Qian Feng, Helena J. Barr, Alicia C. Walker,Lili Xie,Daniel K. Wilton, Indrani Das,Larry I. Benowitz,Beth Stevens
Nature communicationsno. 1 (2023): 6015-15
Daniel K. Wilton,Kevin Mastro, Molly D. Heller, Frederick W. Gergits,Carly Rose Willing, Jaclyn B. Fahey,Arnaud Frouin,Anthony Daggett,Xiaofeng Gu, Yejin A. Kim,Richard L. M. Faull,Suman Jayadev,
Nature Medicineno. 11 (2023): 2866-2884
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Javier Rueda-Carrasco,Dimitra Sokolova,Sang-Eun Lee,Thomas Childs, Natália Jurčáková,Gerard Crowley,Sebastiaan De Schepper,Judy Z Ge, Joanne I Lachica,Christina E Toomey,Oliver J Freeman,John Hardy,
The EMBO journalno. 19 (2023)
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