Lieberam Ivo, Agalliu Dritan, Nagasawa Takashi, Ericson Johan, Jessell Thomas M
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, New York, New York 10032, USA.
Neuron. 2005 Sep 1;47(5):667-79. doi: 10.1016/j.neuron.2005.08.011.
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.
在脊椎动物中枢神经系统的神经元中，运动神经元是唯一将轴突延伸出神经管以支配外周靶标的神经元。两类运动神经元，即腹侧运动神经元（vMNs）和背侧运动神经元（dMNs），分别根据其同源结构域转录因子组成，通过腹侧和背侧出口点将轴突延伸出神经管。在这些转录编码的下游，尚未确定塑造初始运动轴突轨迹的细胞表面受体。我们在此表明，趋化因子受体Cxcr4在vMNs轴突沿着腹侧轨迹延伸时表达，而其配体Cxcl12则由腹侧神经管周围的间充质细胞表达。遗传学研究表明，Cxcl12 - Cxcr4信号传导指导脊髓vMNs的腹侧轨迹。在缺乏该信号时，尽管这些神经元保留了其vMN转录身份，但它们会采用类似dMN的轨迹。因此，Cxcr4信号传导状态有助于确定哺乳动物运动神经元的初始轴突轨迹。
