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.
journal_name
Cell Repjournal_title
Cell reportsauthors
McWilliams TG,Howard L,Wyatt S,Davies AMdoi
10.1016/j.celrep.2015.02.016subject
Has Abstractpub_date
2015-03-10 00:00:00pages
1443-1449issue
9issn
2211-1247pii
S2211-1247(15)00144-8journal_volume
10pub_type
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