The Human Language—Associated Gene SRPX2 Regulates Synapse Formation and Vocalization in Mice

• Published in: Science (American Association for the Advancement of Science) Vol. 342; no. 6161; pp. 987 - 991
• Main Authors: Sia, G. M., Clem, R. L., Huganir, R. L.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 22.11.2013; The American Association for the Advancement of Science
• Subjects: Animal communication; Animals; Biological and medical sciences; Brain; Cerebral cortex; Cerebral Cortex - cytology; Epilepsy - genetics; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Formations; Fundamental and applied biological sciences. Psychology; Gene expression regulation; Genes; Genetic mutation; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Human; Humans; Language; Language Acquisition; Language disorders; Language Disorders - genetics; Language Impairments; Medical sciences; Membrane Proteins; Mice; Mice, Inbred C57BL; Neoplasm Proteins; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Nervous system (semeiology, syndromes); Neurology; Neurons; Neurons - physiology; Proteins; Rats; Rodents; Searching; Synapses; Synapses - physiology; Transfection; Ultrasonics; Vertebrates: nervous system and sense organs; Vocalization; Vocalization, Animal; Human; Nervous system diseases; Cerebral cortex; Synaptogenesis; Pathogenesis; Epilepsy; Rodentia; Central nervous system; Protein; Language disorder; Encephalon; Vertebrata; Synapse; Mammalia; Language; Mouse; Animal; Development; Transcription factor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1245079

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.