title: High content image analysis identifies novel regulators of synaptogenesis in a high-throughput RNAi screen of primary neurons.
abstract: The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors.forename: Thomas J F
authors.initials: TJ
authors.lastname: Nieland
authors.affiliation: Imaging Platform at the Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Logan
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Saulnier
authors.affiliation: RNAi Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lam
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Caroline
authors.initials: C
authors.lastname: Johnson
authors.affiliation: RNAi Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Root
authors.affiliation: Imaging Platform at the Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Carpenter
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
mesh_terms: D000465:Algorithms; D000818:Animals; D057205:Automation, Laboratory; D005786:Gene Expression Regulation; D057166:High-Throughput Screening Assays; D051379:Mice; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering