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Exosomes regulate neurogenesis and circuit assembly.

Pranav Sharma | Pinar Mesci | Cassiano Carromeu | Daniel R McClatchy | Lucio Schiapparelli | John R Yates | Alysson R Muotri | Hollis T Cline
Proceedings of the National Academy of Sciences of the United States of America | 2019

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.

Pubmed ID: 31320591

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH067880
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH103134
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH108528
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH109885
  • Agency: NIMH NIH HHS, United States
    Id: U19 MH107367
  • Agency: NEI NIH HHS, United States
    Id: R01 EY011261
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH100175
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH094753

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