Shift in the function of netrin-1 from axon outgrowth to axon branching in developing cerebral cortical neurons.

Shift in the function of netrin-1 from axon outgrowth to axon branching in developing cerebral cortical neurons.
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DOI:
10.1186/s12868-017-0392-x
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发表时间:
2017-10-17
期刊:
影响因子:
2.4
通讯作者:
Nagashima M
Nagashima M
中科院分区:
医学4区
文献类型:
--
作者:
Matsumoto H;Nagashima M

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Netrin-1是一种多功能轴突导向因子,通过其在结肠直肠癌(DCC)中缺失的受体之一,在几种类型的神经元(包括胚胎小鼠的大脑皮层神经元)中促进轴突生长。然而,我们和其他人已经观察到新生仓鼠的皮质培养物中轴突分支的从头形成,而没有netrin-1诱导的轴突生长。这些先前的报告表明netrin-1功能可能在发育过程中发生变化,我们在这里使用从胚胎小鼠大脑皮层制备的分离培养物进行了研究。成像分析显示netrin-1诱导的胚胎天(E)14轴突和netrin-1诱导的分支E16轴突的生长。Netrin-1诱发的丝状伪足突起,E16轴突轴上发芽前分支形成,可视化的一种新的方法称为大气扫描电子显微镜。用抗DCC功能阻断抗体治疗影响轴突生长和分支。形态学分析表明,netrin-1在皮质轴突的功能在发展过程中的转变的可能性,从促进生长的分支的形成与丝状伪足突起开始。功能阻断实验表明,DCC可能不仅有助于轴突生长,但分支。
Netrin-1, a multifunctional axon guidance cue, elicits axon outgrowth via one of its receptors deleted in colorectal cancer (DCC) in several types of neurons, including cerebral cortical neurons of embryonic mice. However, we and others have observed de novo formation of axon branches without axon outgrowth induced by netrin-1 in cortical culture of neonatal hamsters. These previous reports suggested the possibility that netrin-1 function might alter during development, which we here investigated using dissociated culture prepared from cerebral cortices of embryonic mice. Imaging analysis revealed netrin-1-induced outgrowth in embryonic day (E) 14 axons and netrin-1-induced branching in E16 axons. Netrin-1-evoked filopodial protrusions, which sprouted on the shafts of E16 axons preceding branch formation, were visualized by a novel method called atmospheric scanning electron microscopy. Treatment with an anti-DCC function-blocking antibody affected both axon outgrowth and branching. Morphological analyses suggested a possibility of a shift in the function of netrin-1 in cortical axons during development, from promotion of outgrowth to promotion of branch formation starting with filopodial protrusion. Function-blocking experiments suggested that DCC may contribute not only to axon outgrowth but branching.
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