Netrin (UNC-6) mediates dendritic self-avoidance.

Netrin (UNC-6) mediates dendritic self-avoidance.
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DOI:
10.1038/nn.3065
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发表时间:
2012-03-18
影响因子:
25
通讯作者:
--
中科院分区:
医学1区
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来自单个神经元的树突可能是高度分支的,但通常不重叠。这种自我回避行为已被证明依赖于触发相互排斥的细胞特异性膜蛋白。在这里,我们报告了一个令人惊讶的发现,即线虫中需要一种可扩散的线索,即轴突引导蛋白 UNC-6/Netrin,来自我避免来自 PVD ​​伤害性神经元的姐妹树突。我们使用延时成像来显示,在没有 UNC-6/Netrin 信号传导的情况下,树突在相互接触时无法撤回。我们提出了一个模型,其中 UNC-40/DCC 受体在生长的树突尖端捕获 UNC-6/Netrin,与相对分支上的 UNC-5 相互作用,从而诱导相互排斥。 UNC-40/DCC 还通过独立于 UNC-6/Netrin 的附加途径对树突接触做出反应。我们的研究结果为进化上保守的形态发生线索及其同源受体如何塑造树突结构的基本特征提供了一个新模型。
Dendrites from a single neuron may be highly branched but typically do not overlap. This self-avoidance behavior has been shown to depend on cell-specific membrane proteins that trigger mutual repulsion. Here we report the surprising discovery that a diffusible cue, the axon guidance protein UNC-6/Netrin, is required for self-avoidance of sister dendrites from the PVD nociceptive neuron in C. elegans. We used time lapse imaging to show that dendrites fail to withdraw upon mutual contact in the absence of UNC-6/Netrin signaling. We propose a model in which the UNC-40/DCC receptor captures UNC-6/Netrin at the tips of growing dendrites for interaction with UNC-5 on the apposing branch to induce mutual repulsion. UNC-40/DCC also responds to dendritic contact through an additional pathway that is independent of UNC-6/Netrin. Our findings offer a new model for how an evolutionarily conserved morphogenic cue and its cognate receptors can pattern a fundamental feature of dendritic architecture.
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