Regulation of autocrine signaling in subsets of sympathetic neurons has regional effects on tissue innervation

Thomas G. McWilliams, Laura Howard, Sean Wyatt, Alun M. Davies (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    The regulation of innervation by target-derived factors like nerve growth factor (NGF) is the cornerstone of neurotrophic theory. Whereas autocrine signaling in neurons affecting survival and axon growth has been described, it is difficult to reconcile autocrine signaling with the idea that targets control their innervation. Here, we report that an autocrine signaling loop in developing mouse sympathetic neurons involving CD40L (TNFSF5) and CD40 (TNFRSF5) selectively enhances NGF-promoted axon growth and branching, but not survival, via CD40L reverse signaling. Because NGF negatively regulates CD40L and CD40 expression, this signaling loop operates only in neurons exposed to low levels of NGF. Consequently, the sympathetic innervation density of tissues expressing low NGF is significantly reduced in CD40-deficient mice, whereas the innervation density of tissues expressing high levels of NGF is unaffected. Our findings reveal how differential regulation of autocrine signaling in neurons has region-specific effects on axon growth and tissue innervation.

    Original languageEnglish
    Pages (from-to)1443-1449
    Number of pages7
    JournalCell Reports
    Volume10
    Issue number9
    DOIs
    Publication statusPublished - 10 Mar 2015

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