The Wnt5/Planar Cell Polarity Pathway Regulates Axonal Development of the Drosophila Mushroom Body Neuron
The Wnt5/Planar Cell Polarity Pathway Regulates Axonal Development of the Drosophila Mushroom Body Neuron
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DOI：
10.1523/jneurosci.0154-11.2011
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发表时间：
2011-03-30
影响因子：
5.3
通讯作者：
Tabata, Tetsuya
中科院分区：
文献类型：
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作者：
Shimizu, Kazumichi;Sato, Makoto;Tabata, Tetsuya
轴突发育是神经系统中回路形成的基本过程，并且依赖于许多细胞事件，包括轴突起始、伸长、引导和分支。这些事件背后的分子机制已经得到了很好的研究，特别是轴突的指导。在存在引导信号的情况下，生长锥的极化先于转向反应，这是细胞极性的多种形式的一个例子。平面单元极性（PCP）是单元极性的另一个示例。虽然脊椎动物轴突束的形成需要一些PCP基因，但这些基因是否共同参与PCP通路仍不清楚。在这里，我们表明，基本的PCP信号组件，编码的卷曲（FZ），斜视（STBM），火烈鸟（FMI），乱糟糟的（DSH），是合作所需的轴突靶向和分支的果蝇蘑菇体（MB）神经元。对这些突变体的详细分析表明，这些成分是正确靶向和轴突分叉所必需的。此外，我们认为Wnt 5在PCP途径中起配体的作用。Wnt5突变体在单细胞水平上表现出与PCP突变体相似的表型，并与PCP基因发生遗传相互作用。Wnt 5在发育中的脑中广泛表达。我们建议，Wnt5和PCP途径协调调节轴突的MB的发展。
Axonal development is a fundamental process for circuit formation in the nervous system and is dependent on many cellular events, including axon initiation, elongation, guidance, and branching. The molecular mechanisms underlying these events have been well studied, especially for axon guidance. In the presence of a guidance cue, the polarization of a growth cone precedes the turning response, which is one example of the diverse forms of cell polarity. Planar cell polarity (PCP) is another example of cell polarity. Although some PCP genes are required for axonal tract formation in vertebrates, it remains elusive whether these genes participate in a common PCP pathway concertedly. Here, we show that essential PCP signaling components, encoded by frizzled (fz), strabismus (stbm), flamingo (fmi), and dishevelled (dsh), are cooperatively required for axonal targeting and branching of the Drosophila mushroom body (MB) neurons. A detailed analysis of these mutants revealed that these components were required for the correct targeting and bifurcation of axons. In addition, we suggest that Wnt5 functions as a ligand in the PCP pathway in this process. Wnt5 mutants showed similar phenotypes to PCP mutants at the single-cell level and genetically interacted with PCP genes. Wnt5 was broadly expressed in the developing brain. We propose that Wnt5 and the PCP pathway concertedly regulate axonal development of the MB.