Formation of neuronal dendrite branches: the role of actin nucleators

正确的神经元树突形态的建立对于神经系统的适当连接和信息处理是至关重要的。事实上，树突组织的缺陷与神经系统功能障碍有关。尽管如此，树突复杂和神经元型特定形态形成的基本机制仍远未被了解。在这里，我们建议调查哪些肌动蛋白核因子的组合参与了树突分支的形成，这是一个高度动态的过程。为此，我们将使用一组描述良好的神经元，即果蝇胚胎和幼虫周围神经系统的DA神经元。我们将使用一种改进肌动蛋白保存的技术，将遗传和RNAi介导的基因沉默与体内延时研究和电子显微镜相结合。我们的目标是检查果蝇中所有潜在的肌动蛋白核因子，通过功能丧失和功能获得的实验确定它们在树突分支中的作用，并将这些信息放在电子显微镜提供的结构描述的背景下。我们相信，这种方法的结合将产生体内肌动蛋白核仁复合体在树突分支形成过程中的功能模型。

The establishment of correct neuronal dendrite morphology is essential for appropriate connectivity and information processing in the nervous system. In fact, defects in dendrite organization correlate with nervous system dysfunction. Nonetheless, the basic mechanisms underlying the formation of the complex and neuronal-type specific morphology of dendrites are still far from understood. Here, we propose to investigate which combinations of actin nucleators are involved in the formation of dendritic branches, a highly dynamic process. To this aim, we will use a well described group of neurons, the da neurons of the embryonic and larval peripheral nervous system of Drosophila. We will combine genetic and RNAi-mediated gene silencing with in vivo time-lapse studies and electron-microscopy, using a technique for improved actin preservation. Our goal is to examine all potential actin nucleators in Drosophila, establish their role in dendrite branching by loss- and gain-of-function experiments and to put this information into the context of the structural description provided by the electron-microscopy. We are confident that this combination of approaches will yield models of the function of actin nucleator complexes in vivo during the formation of dendrite branches.