Dscam guides embryonic axons by Netrin-dependent and -independent functions.
Dscam guides embryonic axons by Netrin-dependent and -independent functions.
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DOI：
10.1242/dev.023739
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Kidd T
中科院分区：
文献类型：
--
作者：
Andrews GL;Tanglao S;Farmer WT;Morin S;Brotman S;Berberoglu MA;Price H;Fernandez GC;Mastick GS;Charron F;Kidd T
发育中的轴突被Netrin蛋白和其他未知信号吸引到中枢神经系统的中线。网织蛋白信号部分由FRAZZLED(Fra)/DCC受体转导。对果蝇的遗传分析表明，需要更多的未知受体来介导对Netrin的诱人反应。对Bolwig的神经分析显示，Netrin突变体与唐氏综合症细胞黏附分子(DSCAM)突变体具有相似的表型。Netrin和Dscam突变体表现出剂量敏感的相互作用，提示Dscam可能作为Netrin受体。我们使用细胞覆盖分析表明，Netrin与苍蝇和脊椎动物Dscam结合，Dscam与Netrin结合的亲和力与DCC相同。在CNS中线，我们发现Dscam及其Paralog Dscam3冗余地作用于促进中线交叉。两个Dscam和Netrin受体fra的同时基因敲除产生了一个中线交叉缺陷，比Netrins的去除更强，这表明Dscam也在平行于netrins的途径中发挥作用。此外，在正常情况下不穿过中线的轴突中，Dscam的过度表达能够诱导异位中线交叉，这与吸引人的受体功能一致。我们的结果支持Dscam作为Netrin的有吸引力的受体，也与Frazzed/DCC平行发挥作用的模型。此外，结果表明，Dscam具有对多个配体做出反应的能力，并作为未知中线吸引线索的受体。这些轴突引导功能对唐氏综合征的发病机制有一定的意义。
Developing axons are attracted to the CNS midline by Netrin proteins and other as yet unidentified signals. Netrin signals are transduced in part by Frazzled (Fra)/DCC receptors. Genetic analysis in Drosophila indicates that additional unidentified receptors are needed to mediate the attractive response to Netrin. Analysis of Bolwig’s Nerve reveals that Netrin mutants have a similar phenotype to Down Syndrome Cell Adhesion Molecule (Dscam) mutants. Netrin and Dscam mutants display dose sensitive interactions suggesting that Dscam could act as a Netrin receptor. We show using cell overlay assays that Netrin binds to fly and vertebrate Dscam, and that Dscam binds Netrin with the same affinity as DCC. At the CNS midline, we find that Dscam and its paralog Dscam3 act redundantly to promote midline crossing. Simultaneous genetic knockout of the two Dscams and the Netrin receptor fra produces a midline crossing defect that is stronger than the removal of Netrins, suggesting that Dscams also function in a pathway parallel to Netrins. Additionally, over-expression of Dscam in axons that do not normally cross the midline is able to induce ectopic midline crossing, consistent with an attractive receptor function. Our results support the model that Dscams function as attractive receptors for Netrin and also act in parallel to Frazzled/DCC. Furthermore, the results suggest that Dscams have the ability to respond to multiple ligands and act as receptors for an unidentified midline attractive cue. These functions in axon guidance have implications for the pathogenesis of Down Syndrome.
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DOI：
10.1016/s0006-291x(02)00307-8
发表时间：
2002-05-10
影响因子：
3.1
作者：
Barlow, GM;Micales, B;Korenberg, JR
通讯作者：
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影响因子：
64.5
作者：
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影响因子：
64.5
作者：
Charron, F;Stein, E;Tessier-Lavigne, M
通讯作者：
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影响因子：
4.6
作者：
Forsthoefel, DJ;Liebl, EC;Seeger, MA
通讯作者：
Seeger, MA
DOI：
10.1016/s0169-328x(00)00108-x
发表时间：
2000-06-23
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Agarwala, KL;Nakamura, S;Yamakawa, K
通讯作者：
Yamakawa, K