Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Cell Rep. 2017 Oct 24;21(4):867-877. doi: 10.1016/j.celrep.2017.10.004.
Control of movement relies on the ability of circuits within the spinal cord to establish connections with specific subtypes of motor neuron (MN). Although the pattern of output from locomotor networks can be influenced by MN position and identity, whether MNs exert an instructive role in shaping synaptic specificity within the spinal cord is unclear. We show that Hox transcription-factor-dependent programs in MNs are essential in establishing the central pattern of connectivity within the ventral spinal cord. Transformation of axially projecting MNs to a limb-level lateral motor column (LMC) fate, through mutation of the Hoxc9 gene, causes the central afferents of limb proprioceptive sensory neurons to target MNs connected to functionally inappropriate muscles. MN columnar identity also determines the pattern and distribution of inputs from multiple classes of premotor interneurons, indicating that MNs broadly influence circuit connectivity. These findings indicate that MN-intrinsic programs contribute to the initial architecture of locomotor circuits.
运动的控制依赖于脊髓内的电路与特定类型的运动神经元(MN)建立连接的能力。虽然运动网络的输出模式可能受到 MN 位置和身份的影响,但 MN 是否在塑造脊髓内突触特异性方面发挥指导作用尚不清楚。我们表明,MN 中的 Hox 转录因子依赖性程序对于建立腹侧脊髓内的连接性中枢模式至关重要。通过突变 Hoxc9 基因,将轴向投射的 MN 转化为肢体水平的外侧运动柱(LMC)命运,导致肢体本体感觉感觉神经元的中枢传入纤维将目标定位于与功能不适当的肌肉相连的 MN。MN 柱状身份也决定了来自多种运动前中间神经元的输入的模式和分布,表明 MN 广泛影响电路连接。这些发现表明 MN 内在程序有助于运动电路的初始架构。