Dasen Jeremy S, Liu Jeh-Ping, Jessell Thomas M
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, New York 10032, USA.
Nature. 2003 Oct 30;425(6961):926-33. doi: 10.1038/nature02051.
The organization of neurons into columns is a prominent feature of central nervous system structure and function. In many regions of the central nervous system the grouping of neurons into columns links cell-body position to axonal trajectory, thus contributing to the establishment of topographic neural maps. This link is prominent in the developing spinal cord, where columnar sets of motor neurons innervate distinct targets in the periphery. We show here that sequential phases of Hox-c protein expression and activity control the columnar differentiation of spinal motor neurons. Hox expression in neural progenitors is established by graded fibroblast growth factor signalling and translated into a distinct motor neuron Hox pattern. Motor neuron columnar fate then emerges through cell autonomous repressor and activator functions of Hox proteins. Hox proteins also direct the expression of genes that establish motor topographic projections, thus implicating Hox proteins as critical determinants of spinal motor neuron identity and organization.
神经元排列成柱状是中枢神经系统结构和功能的一个显著特征。在中枢神经系统的许多区域,神经元聚集成柱状将细胞体位置与轴突轨迹联系起来,从而有助于建立拓扑神经图谱。这种联系在发育中的脊髓中很突出,在那里,运动神经元的柱状集合支配外周的不同靶点。我们在此表明,Hox-c蛋白表达和活性的连续阶段控制着脊髓运动神经元的柱状分化。神经祖细胞中的Hox表达通过成纤维细胞生长因子信号的梯度建立,并转化为独特的运动神经元Hox模式。然后,运动神经元的柱状命运通过Hox蛋白的细胞自主抑制和激活功能而出现。Hox蛋白还指导建立运动拓扑投射的基因的表达,因此表明Hox蛋白是脊髓运动神经元身份和组织的关键决定因素。