title: The human language-associated gene SRPX2 regulates synapse formation and vocalization in mice.
abstract: Synapse formation in the developing brain depends on the coordinated activity of synaptogenic proteins, some of which have been implicated in a number of neurodevelopmental disorders. Here, we show that the sushi repeat-containing protein X-linked 2 (SRPX2) gene encodes a protein that promotes synaptogenesis in the cerebral cortex. In humans, SRPX2 is an epilepsy- and language-associated gene that is a target of the foxhead box protein P2 (FoxP2) transcription factor. We also show that FoxP2 modulates synapse formation through regulating SRPX2 levels and that SRPX2 reduction impairs development of ultrasonic vocalization in mice. Our results suggest FoxP2 modulates the development of neural circuits through regulating synaptogenesis and that SRPX2 is a synaptogenic factor that plays a role in the pathogenesis of language disorders.
authors.affiliation: Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Sia
authors.forename: R L
authors.initials: RL
authors.lastname: Clem
authors.forename: R L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology; D004827:Epilepsy / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007802:Language; D007806:Language Disorders / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014162:Transfection; D014828:Vocalization, Animal
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C116881:SRPX2 protein, human