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Wnt5a mediates nerve growth factor-dependent axonal branching
and growth in developing sympathetic neurons.
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 1193661
Author(s) Bodmer,Daniel; Levine-Wilkinson,Seamus; Richmond,Alissa; Hirsh,Sarah; Kuruvilla,Rejji
Author(s) at UniBasel Bodmer, Daniel;
Year 2009
Title Wnt5a mediates nerve growth factor-dependent axonal branching and growth in developing sympathetic
neurons.
Journal J NEUROSCI
Volume 29
Pages / Article-Number 7569-81
Nerve growth factor (NGF) is a potent survival and axon growth factor for neuronal populations in the
peripheral nervous system. Although the mechanisms by which target-derived NGF influences survival of
innervating neurons have been extensively investigated, its regulation of axonal growth and target innervation
are just being elucidated. Here, we identify Wnt5a, a member of the Wnt family of secreted growth factors, as
a key downstream effector of NGF in mediating axonal branching and growth in developing sympathetic
neurons. Wnt5a is robustly expressed in sympathetic neurons when their axons are innervating NGFexpressing targets. NGF:TrkA signaling enhances neuronal expression of Wnt5a. Wnt5a rapidly induces axon
branching while it has a long-term effect on promoting axon extension. Loss of Wnt5a function revealed that it
is necessary for NGF-dependent axonal branching and growth, but not survival, in vitro. Furthermore, Wnt5a(/-) mice display reduced innervation of NGF-expressing target tissues, and a subsequent increase in neuronal
apoptosis, in vivo. Wnt5a functions in developing sympathetic neurons by locally activating protein kinase C in
axons. Together, our findings define a novel regulatory pathway in which Wnt5a, expressed in sympathetic
neurons in response to target-derived NGF, regulates innervation of peripheral targets.
ISSN/ISBN 0270-6474
Full Text on edoc
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/19515925