Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
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果蝇 Netrin-B 控制蘑菇体轴突延伸并调节果蝇脆性 X 综合征模型的求偶相关学习和记忆
DOI：
10.1186/s13041-019-0472-1
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发表时间：
2019-05
期刊：
影响因子：
3.6
通讯作者：
Duan Ranhui
中科院分区：
文献类型：
--
作者：
Kang Huaixing;Zhao Juan;Jiang Xuan;Li Guangxu;Huang Wen;Cheng Huili;Duan Ranhui
蘑菇体（Mushroom body，MB）是果蝇脑内一个重要的嗅觉学习记忆结构。MB的发展涉及轴突叶和姐妹轴突分支的适当引导。准确塑造MB发育的适当指导需要整合由一系列细胞类型提供的各种指导线索，这些细胞类型指导轴突到达MB神经柱内的最终位置。Netrins是轴突导向分子，是胚胎神经索图案形成的保守调节剂。然而，它们是否有助于MB形态发生尚未得到评价。在这里，我们发现Netrin-B（NetB）在MB叶中高度表达，通过与受体Frazzled和Uncoordinated-5的遗传相互作用调节叶长度，从蛹形成后24小时开始。我们观察到NetB的过表达导致MB中严重的β叶融合，这类似于在脆性X综合征（FXS）的果蝇模型中观察到的MB缺陷。我们的研究结果进一步表明，脆性X智力低下蛋白FMRP抑制人类直系同源物Netrin-1（NTN 1）的翻译活性。在FXS模型果蝇中，NetB的敲低显著挽救MB缺陷并改善学习和记忆的缺陷。这些结果表明NetB在MB叶延伸中的关键作用，并将NetB确定为有助于学习和记忆的FMRP的新靶标。
Mushroom body (MB) is a prominent structure essential for olfactory learning and memory in the Drosophila brain. The development of the MB involves the appropriate guidance of axon lobes and sister axon branches. Appropriate guidance that accurately shapes MB development requires the integration of various guidance cues provided by a series of cell types, which guide axons to reach their final positions within the MB neuropils. Netrins are axonal guidance molecules that are conserved regulators of embryonic nerve cord patterning. However, whether they contribute to MB morphogenesis has not yet been evaluated. Here, we find that Netrin-B (NetB) is highly expressed in the MB lobes, regulating lobe length through genetic interactions with the receptors Frazzled and Uncoordinated-5 from 24 h after pupal formation onwards. We observe that overexpression of NetB causes severe β lobe fusion in the MB, which is similar to the MB defects seen in the Drosophila model of fragile X syndrome (FXS). Our results further show that fragile-X mental retardation protein FMRP inhibits the translational activity of human ortholog Netrin-1 (NTN1). Knock-down of NetB significantly rescues the MB defects and ameliorates deficits in the learning and memory in FXS model Drosophila. These results indicate a critical role for NetB in MB lobe extension and identify NetB as a novel target of FMRP which contributes to learning and memory.
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DOI：
10.1016/j.tig.2017.07.008
发表时间：
2017-10
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Davis JK;Broadie K
通讯作者：
Broadie K
影响因子：
11.8
作者：
C. Oliva;A. Soldano;Natalia Mora;N. de Geest;Annelies Claeys;Maria-Luise Erfurth;J. Sierralta;A. Ramaekers;Dan Dascenco;R. Ejsmont;D. Schmucker;N. Sánchez-Soriano;Bassem A. Hassan
通讯作者：
C. Oliva;A. Soldano;Natalia Mora;N. de Geest;Annelies Claeys;Maria-Luise Erfurth;J. Sierralta;A. Ramaekers;Dan Dascenco;R. Ejsmont;D. Schmucker;N. Sánchez-Soriano;Bassem A. Hassan
影响因子：
5.3
作者：
L. Zwarts;T. Goossens;J. Clements;Y. Kang;P. Callaerts
通讯作者：
L. Zwarts;T. Goossens;J. Clements;Y. Kang;P. Callaerts
DOI：
10.1523/jneurosci.3183-13.2014
发表时间：
2014-04
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Brian O. Orr;Melissa A Borgen;Phyllis M Caruccio;R. Murphey
通讯作者：
Brian O. Orr;Melissa A Borgen;Phyllis M Caruccio;R. Murphey
影响因子：
5.3
作者：
Goldman, Jennifer S.;Ashour, Mohammed A.;Kennedy, Timothy E.
通讯作者：
Kennedy, Timothy E.