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

Songlin Li, Esther H. Nie, Yuqin Yin, Larry I. Benowitz, Spencer Tung, Harry V. Vinters, F. Rena Bahjat, Mary P. Stenzel-Poore, Riki Kawaguchi, Giovanni Coppola, S. Thomas Carmichael

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1737-1745
Number of pages9
JournalNature Neuroscience
Volume18
Issue number12
DOIs
StatePublished - Nov 25 2015

ASJC Scopus subject areas

  • Neuroscience(all)

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    Li, S., Nie, E. H., Yin, Y., Benowitz, L. I., Tung, S., Vinters, H. V., Bahjat, F. R., Stenzel-Poore, M. P., Kawaguchi, R., Coppola, G., & Carmichael, S. T. (2015). GDF10 is a signal for axonal sprouting and functional recovery after stroke. Nature Neuroscience, 18(12), 1737-1745. https://doi.org/10.1038/nn.4146