Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1
Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1
复制标题
DOI：
10.1016/j.cell.2008.06.019
复制
发表时间：
2008-07-25
期刊：
影响因子：
64.5
通讯作者：
Jessell, Thomas M.
中科院分区：
文献类型：
--
作者：
Dasen, Jeremy S.;De Camilli, Alessandro;Jessell, Thomas M.
运动神经元支配目标肌肉的精确性取决于一个由Hox转录因子组成的调控网络，该网络将神经元特性转化为连接模式。我们发现，单个转录因子FoxP1通过其作为Hox辅助因子的活性来协调运动神经元亚型特性和连接。FoxP1在对Hox敏感的运动柱中表达，并作为柱状命运的剂量依赖性决定因素。Foxp1失活会消除运动神经元Hox网络的输出，使脊髓运动系统恢复到原始状态。FoxP1的缺失也会改变运动神经元连接的模式，并且在肢体中运动轴突似乎随机选择其轨迹和肌肉目标。我们的研究结果表明，FoxP1是运动神经元多样化和连接的关键决定因素，并阐明了这个Hox调控网络如何控制地形神经图谱的形成。
The precision with which motor neurons innervate target muscles depends on a regulatory network of Hox transcription factors that translates neuronal identity into patterns of connectivity. We show that a single transcription factor, FoxP1, coordinates motor neuron subtype identity and connectivity through its activity as a Hox accessory factor. FoxP1 is expressed in Hox-sensitive motor columns and acts as a dose-dependent determinant of columnar fate. Inactivation of Foxp1 abolishes the output of the motor neuron Hox network, reverting the spinal motor system to an ancestral state. The loss of FoxP1 also changes the pattern of motor neuron connectivity, and in the limb motor axons appear to select their trajectories and muscle targets at random. Our findings show that FoxP1 is a crucial determinant of motor neuron diversification and connectivity, and clarify how this Hox regulatory network controls the formation of a topographic neural map.