DWnt4 regulates the dorsoventral specificity of retinal projections in the Drosophila melanogaster visual system
DWnt4 regulates the dorsoventral specificity of retinal projections in the Drosophila melanogaster visual system
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DOI：
10.1038/nn1604
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发表时间：
2006-01-01
影响因子：
25
通讯作者：
Tabata, T
中科院分区：
文献类型：
--
作者：
Sato, M;Umetsu, D;Tabata, T
在果蝇中，视网膜光感受器细胞的轴突延伸到第一个视神经节--板层，形成了一个地形图。在这里，我们证明了DWNT4，WNT家族的一种分泌蛋白，是椎板的腹侧线索。在DWNT4突变体中，视网膜腹侧轴突错误地投射到背板。DWNT4在发育中的板层腹侧半部正常表达，沿视网膜腹侧轴突检测到DWNT4蛋白。DFrizzled2和Disheveled分别编码Wnt信号所需的受体和信号分子。这两个基因的突变都导致了DWNT4样的缺陷，而且这两个基因在视网膜中都是自主需要的，这表明DWNT4在视网膜轴突指导中发挥了直接作用。相比之下，易洛魁人的同源盒基因是视网膜的背部信号。在易洛魁突变体中，背侧轴突积累了DWnt4并错误地投射到腹板；在易洛魁DFrizzled2突变体中，这种表型被抑制，这表明易洛魁可能减弱了DFrizzled2对DWnt4的应答能力。
In Drosophila melanogaster, the axons of retinal photoreceptor cells extend to the first optic ganglion, the lamina, forming a topographic representation. Here we show that DWnt4, a secreted protein of the Wnt family, is the ventral cue for the lamina. In DWnt4 mutants, ventral retinal axons misprojected to the dorsal lamina. DWnt4 was normally expressed in the ventral half of the developing lamina and DWnt4 protein was detected along ventral retinal axons. Dfrizzled2 and dishevelled, respectively, encode a receptor and a signaling molecule required for Wnt signaling. Mutations in both genes caused DWnt4-like defects, and both genes were autonomously required in the retina, suggesting a direct role of DWnt4 in retinal axon guidance. In contrast, iroquois homeobox genes are the dorsal cues for the retina. Dorsal axons accumulated DWnt4 and misprojected to the ventral lamina in iroquois mutants; the phenotype was suppressed in iroquois Dfrizzled2 mutants, suggesting that iroquois may attenuate the competence of Dfrizzled2 to respond to DWnt4.