TY - JOUR T1 - Exosomes regulate Neurogenesis and Circuit Assembly in a Model of Rett Syndrome JF - bioRxiv DO - 10.1101/168955 SP - 168955 AU - Pranav Sharma AU - Pinar Mesci AU - Cassiano Carromeu AU - Daniel McClatchy AU - Lucio Schiapparelli AU - John R Yates III AU - Alysson R. Muotri AU - Hollis T Cline Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/26/168955.abstract N2 - Exosomes are thought to be secreted by all cells in the body and to be involved in intercellular communication. Here, we tested whether neural exosomes regulate the development of neural circuits and whether exosome-mediated signaling may be aberrant in the neurodevelopmental disorder Rett Syndrome (RTT). Quantitative proteomic analysis comparing exosomes from human induced pluripotent stem cells (hiPSC) - derived RTT patient or control neural cultures indicates that control exosomes contain signaling components capable of influencing neuronal development and function, which are lacking in RTT exosomes. Moreover, treatment with control exosomes rescues neuron number, apoptosis, synaptic puncta and synchronized firing phenotypes of MeCP2 knockdown in human primary neurons, indicating that exosomes have the capacity to influence neural development and may be a promising avenue to treat neurodevelopmental disorders like Rett Syndrome.Highlights Exosome proteomics distinguish cargo in RTT vs control hiPSC-derived neural cultures Control but not RTT exosomes increase neurogenesis in human neural cultures hiPSC-derived neural exosomes reverse pathological phenotypes in RTT neural cultures RTT exosomes do not impair neural development ER -