Stem cell factor functions as an outgrowth-promoting factor to enable axon exit from the midline intermediate target

Stem cell factor functions as an outgrowth-promoting factor to enable axon exit from the midline intermediate target
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DOI:
10.1016/j.neuron.2008.01.006
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发表时间:
2008-02-28
期刊:
影响因子:
16.2
通讯作者:
Tessier-Lavigne, Marc
Tessier-Lavigne, Marc
中科院分区:
医学1区
文献类型:
--
作者:
Gore, Bryan B.;Wong, Karen G.;Tessier-Lavigne, Marc

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连合轴突被吸引到中线中间目标的化学引诱剂,但在跨越中线他们关闭响应吸引剂和开关的响应中线排斥,从中线驱逐轴突,使他们能够move on.In这里,我们表明,中线出口也需要刺激轴突生长的干细胞因子(SCF,也被称为钢因子)。SCF由中线底板细胞表达,其受体Kit(一种受体酪氨酸激酶)由连合轴突表达。在Steel和Kit突变小鼠中,大多数连合轴突在底板的对侧边缘短暂排列,显示中线出口延迟。在体外,SCF选择性地促进后交叉,但不是前交叉,连合轴突的生长。我们的研究结果将SCF确定为中枢神经系统中的指导信号,并提供证据表明退出中间靶点需要激活促生长机制。
Commissural axons are attracted to the midline intermediate target by chemoattractants, but upon crossing the midline they switch off responsiveness to attractants and switch on responsiveness to midline repellents, which expel the axons from the midline and enable them to move on. Here we show that midline exit also requires the stimulation of axon outgrowth by Stem Cell Factor (SCF, also known as Steel Factor). SCF is expressed by midline floor plate cells, and its receptor Kit, a receptor tyrosine kinase, is expressed by commissural axons. In Steel and Kit mutant mice, the majority of commissural axons line up transiently at the contralateral edge of the floor plate, showing a delay in midline exit. In vitro, SCF selectively promotes outgrowth of postcrossing, but not precrossing, commissural axons. Our findings identify SCF as a guidance cue in the CNS, and provide evidence that exiting intermediate targets requires activation of outgrowth-promoting mechanisms.