Gore Bryan B, Wong Karen G, Tessier-Lavigne Marc
Division of Research, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Neuron. 2008 Feb 28;57(4):501-10. doi: 10.1016/j.neuron.2008.01.006.
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.
连合轴突被化学引诱剂吸引至中线中间靶点，但在穿过中线后，它们会关闭对引诱剂的反应能力，并开启对中线排斥因子的反应能力，这些排斥因子将轴突从中线排出，使其能够继续前行。我们在此表明，中线退出还需要干细胞因子（SCF，也称为Steel因子）刺激轴突生长。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，大多数连合轴突会在底板的对侧边缘短暂排列，显示出中线退出延迟。在体外，SCF选择性地促进穿过中线后的连合轴突生长，而不是穿过中线前的连合轴突生长。我们的研究结果确定SCF为中枢神经系统中的一种导向线索，并提供证据表明离开中间靶点需要激活促进生长的机制。
