Targeting of retinal axons requires the metalloproteinase ADAM10
Targeting of retinal axons requires the metalloproteinase ADAM10
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DOI：
10.1523/jneurosci.1841-07.2007
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发表时间：
2007-08-01
影响因子：
5.3
通讯作者：
McFarlane, Sarah
中科院分区：
文献类型：
--
作者：
Chen, Yuanyuan Y.;Hehr, Carrie L.;McFarlane, Sarah
外部线索在指导轴突发育中的作用已经得到了很好的确立，但是，这些外部线索的活动受到调节的方式却知之甚少。去整合素和金属蛋白酶（adintegrin and metalloproteinase，ADAM）是一种锌依赖性蛋白酶，可以在体外切割引导信号或其受体。在这里，我们确定了第一个例子的金属蛋白酶的功能在脊椎动物轴突的指导在体内。具体地说，ADAM10是非洲爪蟾视网膜神经节细胞（RGC）轴突形成视投射所必需的。Xadam10 mRNA在背侧神经上皮中表达，RGC轴突通过背侧神经上皮延伸。在大脑中对ADAM10的药理学或分子抑制各自导致RGC轴突识别其靶点的失败。相反，在RGC轴突本身内的ADAM10的分子抑制没有影响。这些数据有力地证明，在背侧脑中，ADAM10非自主地作用于细胞以调节RGC轴突的引导。
The role of extrinsic cues in guiding developing axons is well established; however, the means by which the activity of these extrinsic cues is regulated is poorly understood. A disintegrin and metalloproteinase (ADAM) enzymes are Zn-dependent proteinases that can cleave guidance cues or their receptors in vitro. Here, we identify the first example of a metalloproteinase that functions in vertebrate axon guidance in vivo. Specifically, ADAM10 is required for formation of the optic projection by Xenopus retinal ganglion cell (RGC) axons. Xadam10 mRNA is expressed in the dorsal neuroepithelium through which RGC axons extend. Pharmacological or molecular inhibition of ADAM10 within the brain each resulted in a failure of RGC axons to recognize their target. In contrast, molecular inhibition of ADAM10 within the RGC axons themselves had no effect. These data argue strongly that in the dorsal brain ADAM10 acts cell non-autonomously to regulate the guidance of RGC axons.