The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance
The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance
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DOI：
10.1038/nature05090
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发表时间：
2006-09-14
期刊：
影响因子：
64.8
通讯作者：
Jan, Yuh-Nung
中科院分区：
文献类型：
--
作者：
Emoto, Kazuo;Parrish, Jay Z.;Jan, Yuh-Nung
树突状场的精确图案化对于神经元回路的形成和功能是必不可少的，但是神经元在发育过程中如何建立和维持它们的树突状场却知之甚少。在果蝇IV类树突树枝状神经元中，树突平铺，其允许树突区域的完全但非重叠覆盖（1-3），通过由Tricorned（Trc）介导的树突的“类似排斥样”行为建立，Trc是果蝇中两种NDR（核Dbf 2相关）家族激酶之一（4-7）。在这里，我们报道了另一个NDR家族激酶，肿瘤抑制因子Warts/Lats（Wts）（8-10），调节树突的维持;在Wts突变体中，树突最初正常地平铺体壁，但在后期幼虫阶段逐渐失去分支，而轴突没有显示出明显的缺陷。我们进一步提供了肿瘤抑制激酶Hippo（Hpo）（11-15）作为Wts和Trc的上游调节剂分别用于树突维持和平铺的生物化学和遗传学证据，从而揭示了Hpo信号传导途径的肿瘤抑制基因在树突形态发生中的重要功能。
Precise patterning of dendritic fields is essential for neuronal circuit formation and function, but how neurons establish and maintain their dendritic fields during development is poorly understood. In Drosophila class IV dendritic arborization neurons, dendritic tiling, which allows for the complete but nonoverlapping coverage of the dendritic fields(1-3), is established through a 'like-repels-like' behaviour of dendrites mediated by Tricornered (Trc), one of two NDR ( nuclear Dbf2-related) family kinases in Drosophila(4-7). Here we report that the other NDR family kinase, the tumour suppressor Warts/Lats (Wts)(8-10), regulates the maintenance of dendrites; in wts mutants, dendrites initially tile the body wall normally, but progressively lose branches at later larval stages, whereas the axon shows no obvious defects. We further provide biochemical and genetic evidence for the tumour suppressor kinase Hippo (Hpo)(11-15) as an upstream regulator of Wts and Trc for dendrite maintenance and tiling, respectively, thereby revealing important functions of tumour suppressor genes of the Hpo signalling pathway in dendrite morphogenesis.