Neuert Helen, Yuva-Aydemir Yeliz, Silies Marion, Klämbt Christian
Institut für Neurobiologie, Universität Münster, Badestrasse 9, 48149 Münster, Germany.
Institut für Neurobiologie, Universität Münster, Badestrasse 9, 48149 Münster, Germany
Development. 2017 Dec 15;144(24):4673-4683. doi: 10.1242/dev.152694. Epub 2017 Oct 30.
The development of the nervous system requires tight control of cell division, fate specification and migration. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that affects different steps of cell cycle progression, as well as having postmitotic functions in nervous system development. It can therefore link different developmental stages in one tissue. The two adaptor proteins, Fizzy/Cdc20 and Fizzy-related/Cdh1, confer APC/C substrate specificity. Here, we show that two distinct modes of APC/C function act during eye development. Fizzy/Cdc20 controls the early growth of the eye disc anlage and the concomitant entry of glial cells onto the disc. In contrast, acts during neuronal patterning and photoreceptor axon growth, and subsequently affects neuron-glia interaction. To further address the postmitotic role of Fzr/Cdh1 in controlling neuron-glia interaction, we identified a series of novel APC/C candidate substrates. Four of our candidate genes are required for -dependent neuron-glia interaction, including the dynein light chain Taken together, our data show how different modes of APC/C activation can couple early growth and neuron-glia interaction during eye disc development.
神经系统的发育需要对细胞分裂、命运特化和迁移进行严格控制。后期促进复合物/细胞周期体(APC/C)是一种E3泛素连接酶,它影响细胞周期进程的不同步骤,并且在神经系统发育中具有有丝分裂后的功能。因此,它可以将一个组织中的不同发育阶段联系起来。两种衔接蛋白,Fizzy/Cdc20和Fizzy-related/Cdh1,赋予APC/C底物特异性。在这里,我们表明APC/C功能的两种不同模式在眼睛发育过程中发挥作用。Fizzy/Cdc20控制眼盘原基的早期生长以及神经胶质细胞随之进入眼盘。相比之下,Fzr/Cdh1在神经元模式形成和光感受器轴突生长过程中发挥作用,随后影响神经元与神经胶质细胞的相互作用。为了进一步探讨Fzr/Cdh1在控制神经元与神经胶质细胞相互作用中的有丝分裂后作用,我们鉴定了一系列新的APC/C候选底物。我们的四个候选基因是依赖于Fzr/Cdh1的神经元与神经胶质细胞相互作用所必需的,包括动力蛋白轻链。总之,我们的数据表明了APC/C激活的不同模式如何在眼盘发育过程中耦合早期生长和神经元与神经胶质细胞的相互作用。