Rosen, AllisonStevens, Beth2014-07-072014Bialas, 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.3560.1097-6256http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406754Immune 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.en-USJournal Article2014-07-0710.1038/nn.3560