TGF-β Signaling Regulates Neuronal C1q Expression and Developmental Synaptic Refinement

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TGF-β Signaling Regulates Neuronal C1q Expression and Developmental Synaptic Refinement

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Title: TGF-β Signaling Regulates Neuronal C1q Expression and Developmental Synaptic Refinement
Author: Bialas, Allison R.; Stevens, Beth

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Citation: Bialas, Allison R., and Beth Stevens. 2014. “TGF-β Signaling Regulates Neuronal C1q Expression and Developmental Synaptic Refinement.” Nature neuroscience 16 (12): 1773-1782. doi:10.1038/nn.3560. http://dx.doi.org/10.1038/nn.3560.
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Abstract: Immune molecules, including complement proteins C1q and C3, have emerged as critical mediators of synaptic refinement and plasticity. Complement localizes to synapses and refines the developing visual system via C3-dependent microglial phagocytosis of synapses. Retinal ganglion cells (RGCs) express C1q, the initiating protein of the classical complement cascade, during retinogeniculate refinement; however, the signals controlling C1q expression and function remain elusive. Previous work implicated an astrocyte-derived factor in regulating neuronal C1q expression. Here we identify retinal TGF-β as a key regulator of neuronal C1q expression and synaptic pruning in the developing visual system. Mice lacking TGF-β receptor II (TGFβRII) in retinal neurons have reduced C1q expression in RGCs, reduced synaptic localization of complement, and phenocopy refinement defects observed in complement-deficient mice, including reduced eye specific segregation and microglial engulfment of RGC inputs. These data implicate TGF-β in regulating neuronal C1q expression to initiate complement- and microglia-mediated synaptic pruning.
Published Version: doi:10.1038/nn.3560
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973738/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406754
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