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GDF10 is a signal for axonal sprouting and functional recovery after stroke.

Nature neuroscience | 2015

Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and differentiation factor 10 (GDF10) is induced in peri-infarct neurons in mice, non-human primates and humans. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI and TGFβRII signaling. Using pharmacogenetic gain- and loss-of-function studies, we found that GDF10 produced axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocked axonal sprouting and reduced recovery. RNA sequencing from peri-infarct cortical neurons revealed that GDF10 downregulated PTEN, upregulated PI3 kinase signaling and induced specific axonal guidance molecules. Using unsupervised genome-wide association analysis of the GDF10 transcriptome, we found that it was not related to neurodevelopment, but may partially overlap with other CNS injury patterns. Thus, GDF10 is a stroke-induced signal for axonal sprouting and functional recovery.

Pubmed ID: 26502261 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: P30 NS062691
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS085019
  • Agency: NINDS NIH HHS, United States
    Id: U01 NS064953
  • Agency: NINDS NIH HHS, United States
    Id: NS086431
  • Agency: NIH HHS, United States
    Id: P51 OD011092
  • Agency: NINDS NIH HHS, United States
    Id: NS085019

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