Draxin, a Repulsive Guidance Protein for Spinal Cord and Forebrain Commissures

Draxin, a Repulsive Guidance Protein for Spinal Cord and Forebrain Commissures
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DOI:
10.1126/science.1165187
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发表时间:
2009-01-16
期刊:
影响因子:
56.9
通讯作者:
Tanaka, Hideaki
Tanaka, Hideaki
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Islam, Shahidul M.;Shinmyo, Yohei;Tanaka, Hideaki

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轴突导向蛋白对于发育期间神经系统的正确布线至关重要。几个轴突导向线索和他们的家庭成员已经得到很好的表征。假设更多未识别的轴突引导线索参与极其复杂的神经系统的形成。我们确定了一种分泌蛋白,draxin,与已知的指导线索没有同源性。Draxin在体外抑制或排斥背侧脊髓和皮质外植体的神经突生长。异位表达的Draxin抑制鸡脊髓连合轴突的生长或导致其走错。Draxin基因敲除小鼠显示脊髓连合轴突的去纤维化和所有前脑连合的缺失。因此,Draxin是一种以前未知的化学排斥性轴突导向分子,是脊髓和前脑连合发育所需的。
Axon guidance proteins are critical for the correct wiring of the nervous system during development. Several axon guidance cues and their family members have been well characterized. More unidentified axon guidance cues are assumed to participate in the formation of the extremely complex nervous system. We identified a secreted protein, draxin, that shares no homology with known guidance cues. Draxin inhibited or repelled neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Ectopically expressed draxin inhibited growth or caused misrouting of chick spinal cord commissural axons in vivo. draxin knockout mice showed defasciculation of spinal cord commissural axons and absence of all forebrain commissures. Thus, draxin is a previously unknown chemorepulsive axon guidance molecule required for the development of spinal cord and forebrain commissures.