Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 32, Pages 16086-16094Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1902513116
Keywords
exosomes; Rett syndrome; neuronal development; synaptogenesis; extracellular vesicle
Categories
Funding
- National Institutes of Health [R01MH108528, R01MH094753, R01MH109885, R01MH100175, U19MH107367]
- SFARI Grant [345469]
- NARSAD Independent Investigator Grant
- International Rett syndrome Foundation (IRSF) fellowship
- NIH [R01MH103134, R01EY011261, 5R01MH067880, 5R01MH100175]
- Hahn Family Foundation
- California Institute of Regenerative Medicine (CIRM) [TG2-01165]
- Helen Dorris Foundation
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Exosomes are thought to be released by all cells in the body and to be involved in intercellular communication. We tested whether neural exosomes can regulate the development of neural circuits. We show that exosome treatment increases proliferation in developing neural cultures and in vivo in dentate gyrus of P4 mouse brain. We compared the protein cargo and signaling bioactivity of exosomes released by hiPSC-derived neural cultures lacking MECP2, a model of the neurodevelopmental disorder Rett syndrome, with exosomes released by isogenic rescue control neural cultures. Quantitative proteomic analysis indicates that control exosomes contain multiple functional signaling networks known to be important for neuronal circuit development. Treating MECP2-knockdown human primary neural cultures with control exosomes rescues deficits in neuronal proliferation, differentiation, synaptogenesis, and synchronized firing, whereas exosomes from MECP2-deficient hiPSC neural cultures lack this capability. These data indicate that exosomes carry signaling information required to regulate neural circuit development.
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