| First Author | Bodmer D | Year | 2009 |
| Journal | J Neurosci | Volume | 29 |
| Issue | 23 | Pages | 7569-81 |
| PubMed ID | 19515925 | Mgi Jnum | J:149814 |
| Mgi Id | MGI:3849208 | Doi | 10.1523/JNEUROSCI.1445-09.2009 |
| Citation | Bodmer D, et al. (2009) Wnt5a mediates nerve growth factor-dependent axonal branching and growth in developing sympathetic neurons. J Neurosci 29(23):7569-81 |
| abstractText | 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 NGF-expressing 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. |
