In Drosophila,the dendritic arborization neurons (ddaC neurons) undergo developmental neurodegeneration to selectively prune their larval dendrites during metamorphosis. Recently we have developed ddaC neurons as a powerful genetic system: 1) to identify novel players and genetic programs of neurodegeneration; 2) to understand cellular mechanisms of neurodegeneration in a single-neuron resolution.
We have identified a novel genetic pathway composed of sox14 and its cytoskeletal target gene mical which governs severing of dendrites during pruning. sox14 encodes a key transcription factor that is necessary and sufficient to mediate dendrite severing during pruning in response to ecdysone signaling. We further discovered that Sox14 mediates dendrite pruning by directly regulating the expression of a novel target gene, mical. mical encodes a large cytosolic protein with multiple domains known to associate with cytoskeletal components. mical mutants showed dramatic severing defects during dendrite pruning, similar to those of sox14 mutants. Overexpression of Mical can significantly rescue pruning defects in sox14 mutants, suggesting that Mical is the major downstream target of Sox14 during pruning. Thus, our findings indicate that a novel pathway composed of Sox14 and its cytoskeletal target Mical governs dendrite severing during pruning.
Reference: Kirilly D., Gu Y., Huang Y., Wu Z., Bashirullah A., Low BC, Kolodkin A.L., Wang H. and Yu F. A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning. Nature Neuroscience, in press. |
