The Classical Complement Pathway Mediates Microglia-Dependent Remodeling of Spinal Motor Circuits during Development and in SMA.

ABSTRACT: Movement is an essential behavior requiring the assembly and refinement of spinal motor circuits. However, the mechanisms responsible for circuit refinement and synapse maintenance are poorly understood. Similarly, the molecular mechanisms by which gene mutations cause dysfunction and elimination of synapses in neurodegenerative diseases that occur during development are unknown. Here, we demonstrate that the complement protein C1q is required for the refinement of sensory-motor circuits during normal development, as well as for synaptic dysfunction and elimination in spinal muscular atrophy (SMA). C1q tags vulnerable SMA synapses, which triggers activation of the classical complement pathway leading to microglia-mediated elimination. Pharmacological inhibition of C1q or depletion of micro

SUBMITTER: Vukojicic A 

PROVIDER: S-EPMC6937140 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature