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Fascin 控制神经元类特有的树突分支形态。

Fascin controls neuronal class-specific dendrite arbor morphology.

机构信息

Dendrite Differentiation Group, Department of Molecular Neurobiology, MPI of Neurobiology, 82152 Munich-Martinsried, Germany.

出版信息

Development. 2012 Aug;139(16):2999-3009. doi: 10.1242/dev.077800. Epub 2012 Jul 4.

DOI:10.1242/dev.077800
PMID:22764047
Abstract

The branched morphology of dendrites represents a functional hallmark of distinct neuronal types. Nonetheless, how diverse neuronal class-specific dendrite branches are generated is not understood. We investigated specific classes of sensory neurons of Drosophila larvae to address the fundamental mechanisms underlying the formation of distinct branch types. We addressed the function of fascin, a conserved actin-bundling protein involved in filopodium formation, in class III and class IV sensory neurons. We found that the terminal branchlets of different classes of neurons have distinctive dynamics and are formed on the basis of molecularly separable mechanisms; in particular, class III neurons require fascin for terminal branching whereas class IV neurons do not. In class III neurons, fascin controls the formation and dynamics of terminal branchlets. Previous studies have shown that transcription factor combinations define dendrite patterns; we find that fascin represents a downstream component of such programs, as it is a major effector of the transcription factor Cut in defining class III-specific dendrite morphology. Furthermore, fascin defines the morphological distinction between class III and class IV neurons. In fact, loss of fascin function leads to a partial conversion of class III neurons to class IV characteristics, while the reverse effect is obtained by fascin overexpression in class IV neurons. We propose that dedicated molecular mechanisms underlie the formation and dynamics of distinct dendrite branch types to elicit the accurate establishment of neuronal circuits.

摘要

树突的分支形态代表了不同神经元类型的功能特征。然而,不同神经元类型的特定树突分支是如何产生的还不清楚。我们研究了果蝇幼虫的特定感觉神经元类别,以解决形成不同分支类型的基本机制。我们研究了参与形成丝状伪足的保守肌动蛋白结合蛋白 fascin 在第三类和第四类感觉神经元中的功能。我们发现,不同神经元类型的终末分支具有独特的动力学特征,并基于分子上可分离的机制形成;特别是,第三类神经元需要 fascin 来形成终末分支,而第四类神经元则不需要。在第三类神经元中,fascin 控制终末分支的形成和动力学。先前的研究表明,转录因子组合定义了树突模式;我们发现,fascin 是这些程序的下游组成部分,因为它是转录因子 Cut 定义第三类特定树突形态的主要效应子。此外,fascin 定义了第三类和第四类神经元之间的形态区别。事实上,fascin 功能的丧失导致第三类神经元向第四类特征的部分转化,而 fascin 在第四类神经元中的过表达则获得相反的效果。我们提出,特定的分子机制是形成和动态变化不同树突分支类型的基础,以引发神经元回路的准确建立。

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