A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning
A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning
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DOI：
10.1038/nn.2415
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发表时间：
2009-12-01
影响因子：
25
通讯作者：
Yu, Fengwei
中科院分区：
文献类型：
--
作者：
Kirilly, Daniel;Gu, Ying;Yu, Fengwei
在发育过程中，选择性地去除神经元突起的修剪对于神经回路的精细化至关重要。在果蝇中，Ⅳ类树突分支神经元（ddaC）在变态过程中会经历修剪，以去除其幼虫期的树突。我们鉴定出Sox14是一种转录因子，它对于响应蜕皮激素信号在修剪过程中介导树突切断是必需的且是充分的。我们发现Sox14通过直接调控靶基因mical的表达来介导树突修剪。mical编码一种大型胞质蛋白，其具有多个已知与细胞骨架成分相关的结构域。mical突变体在树突修剪过程中存在明显的切断缺陷，与sox14突变体的缺陷相似。Mical的过表达能够显著挽救sox14突变体中的修剪缺陷，这表明Mical是修剪过程中Sox14的一个主要下游靶标。因此，我们的研究结果表明，一个由Sox14及其细胞骨架靶标Mical组成的先前未知的通路控制着树突切断。
Pruning that selectively eliminates neuronal processes is crucial for the refinement of neural circuits during development. In Drosophila, the class IV dendritic arborization neuron (ddaC) undergoes pruning to remove its larval dendrites during metamorphosis. We identified Sox14 as a transcription factor that was necessary and sufficient to mediate dendrite severing during pruning in response to ecdysone signaling. We found that Sox14 mediated dendrite pruning by directly regulating the expression of the target gene mical. mical encodes a large cytosolic protein with multiple domains that are known to associate with cytoskeletal components. mical mutants had marked severing defects during dendrite pruning that were similar to those of sox14 mutants. Overexpression of Mical could significantly rescue pruning defects in sox14 mutants, suggesting that Mical is a major downstream target of Sox14 during pruning. Thus, our findings indicate that a previously unknown pathway composed of Sox14 and its cytoskeletal target Mical governs dendrite severing.