An interaction screen identifies headcase as a regulator of large-scale pruning.
An interaction screen identifies headcase as a regulator of large-scale pruning.
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DOI：
10.1523/jneurosci.1391-12.2012
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发表时间：
2012-11-28
期刊：
影响因子：
--
通讯作者：
Williams DW
中科院分区：
文献类型：
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作者：
Loncle N;Williams DW
大规模的修剪，长神经元过程的去除，广泛部署在发育中的神经系统，是必要的适当的电路形成。果蝇IV类树突感觉神经元ddaC的树突在类固醇激素蜕皮激素的控制下发生局部退化，从而发生大规模的剪枝。控制这些事件的分子机制在很大程度上是未知的。为了确定协调这种发育退化的新分子，我们进行了基因相互作用筛选。我们的方法结合了果蝇正向遗传学的力量和ddaC神经元的详细体内成像。这一筛选使我们能够确定headcase （hdc）是一个参与树突修剪的新基因。HDC在进化上是保守的，但其功能尚不清楚。在这里，我们发现hdc在经历重塑的感觉神经元的变态之前表达。需要HDC以细胞自主的方式来控制树突切断，这是修剪的第一阶段。我们对已知的树突修剪调节因子的上位性实验表明，hdc是蜕皮激素信号传导下游新途径的创始成员。
Large-scale pruning, the removal of long neuronal processes, is deployed widely within the developing nervous system and is essential for proper circuit formation. In Drosophila the dendrites of the class IV dendritic arborization sensory neuron ddaC undergo large-scale pruning by local degeneration controlled by the steroid hormone ecdysone. The molecular mechanisms that control such events are largely unknown. To identify new molecules that orchestrate this developmental degeneration we performed a genetic interaction screen. Our approach combines the strength of Drosophila forward genetics with detailed in vivo imaging of ddaC neurons. This screen allowed us to identify headcase (hdc) as a new gene involved in dendrite pruning. hdc is evolutionarily conserved, but the protein’s function is unknown. Here we show that hdc is expressed just prior to metamorphosis in sensory neurons that undergo remodeling. hdc is required in a cell autonomous manner to control dendrite severing, the first phase of pruning. Our epistasis experiments with known regulators of dendrite pruning reveal hdc as a founding member of a new pathway downstream of ecdysone signaling.