A Cxcl12-Cxcr4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons
A Cxcl12-Cxcr4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons
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DOI：
10.1016/j.neuron.2005.08.011
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发表时间：
2005-09-01
期刊：
影响因子：
16.2
通讯作者：
Jessell, TM
中科院分区：
文献类型：
--
作者：
Lieberam, I;Agalliu, D;Jessell, TM
在脊椎动物CNS中的神经元中，运动神经元单独地将轴突延伸出神经管以神经支配外周靶。两类运动神经元，称为vMN和dMN，分别通过腹侧和背侧出口点将轴突延伸出神经管，这与它们的同源域转录因子库雅阁。在这些转录编码的下游，形成初始运动轴突轨迹的细胞表面受体尚未被确定。我们在这里表明，趋化因子受体Cxcr 4的vMN的轴突上表达，因为他们遵循其腹侧轨迹，而其配体，Cxcl 12，是由腹侧神经管周围的间充质细胞表达。遗传学研究表明，Cxcl 12-Cxcr 4信号传导指导脊髓vMN的腹侧轨迹。在它的情况下，这些神经元采用dMN样的轨迹，尽管保存他们的vMN转录身份。因此，Cxcr 4信号的状态有助于确定哺乳动物运动神经元的初始轴突轨迹。
Motor neurons, alone among neurons in the vertebrate CNS, extend axons out of the neural tube to innervate peripheral targets. Two classes of motor neurons, termed vMNs and dMNs, extend axons out of the neural tube via ventral and dorsal exit points, respectively, in accord with their homeodomain transcription factor repertoire. Downstream of these transcriptional codes, the cell surface receptors that shape initial motor axon trajectories have not been identified. We show here that the chemokine receptor Cxcr4 is expressed on the axons of vMNs as they follow their ventral trajectory, whereas its ligand, Cxcl12, is expressed by mesenchymal cells surrounding the ventral neural tube. Genetic studies reveal that Cxcl12-Cxcr4 signaling directs the ventral trajectory of spinal vMNs. In its absence, these neurons adopt a dMN-like trajectory, despite preservation of their vMN transcriptional identity. Thus, the status of Cxcr4 signaling helps to determine the initial axonal trajectory of mammalian motor neurons.