| First Author | Chen M | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 39 | Pages | 13439-53 |
| PubMed ID | 23015435 | Mgi Jnum | J:188272 |
| Mgi Id | MGI:5440114 | Doi | 10.1523/JNEUROSCI.2039-12.2012 |
| Citation | Chen M, et al. (2012) Spatially coordinated kinase signaling regulates local axon degeneration. J Neurosci 32(39):13439-53 |
| abstractText | In addition to being a hallmark of neurodegenerative disease, axon degeneration is used during development of the nervous system to prune unwanted connections. In development, axon degeneration is tightly regulated both temporally and spatially. Here, we provide evidence that degeneration cues are transduced through various kinase pathways functioning in spatially distinct compartments to regulate axon degeneration. Intriguingly, glycogen synthase kinase-3 (GSK3) acts centrally, likely modulating gene expression in the cell body to regulate distally restricted axon degeneration. Through a combination of genetic and pharmacological manipulations, including the generation of an analog-sensitive kinase allele mutant mouse for GSK3beta, we show that the beta isoform of GSK3, not the alpha isoform, is essential for developmental axon pruning in vitro and in vivo. Additionally, we identify the dleu2/mir15a/16-1 cluster, previously characterized as a regulator of B-cell proliferation, and the transcription factor tbx6, as likely downstream effectors of GSK3beta in axon degeneration. |
