Thaler Joshua P, Koo Sonya J, Kania Artur, Lettieri Karen, Andrews Shane, Cox Christopher, Jessell Thomas M, Pfaff Samuel L
Gene Expression Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
Neuron. 2004 Feb 5;41(3):337-50. doi: 10.1016/s0896-6273(04)00011-x.
LIM homeobox genes have a prominent role in the regulation of neuronal subtype identity and distinguish motor neuron subclasses in the embryonic spinal cord. We have investigated the role of Isl-class LIM homeodomain proteins in motor neuron diversification using mouse genetic methods. All spinal motor neuron subtypes initially express both Isl1 and Isl2, but Isl2 is rapidly downregulated by visceral motor neurons. Mouse embryos lacking Isl2 function exhibit defects in the migration and axonal projections of thoracic level motor neurons that appear to reflect a cell-autonomous switch from visceral to somatic motor neuron character. Additional genetic mutations that reduce or eliminate both Isl1 and Isl2 activity result in more pronounced defects in visceral motor neuron generation and erode somatic motor neuron character. Thus, an early phase of high Isl expression and activity in newly generated motor neurons permits the diversification of visceral and somatic motor neuron subtypes in the developing spinal cord.
LIM 同源框基因在调节神经元亚型特性方面发挥着重要作用，并可区分胚胎脊髓中的运动神经元亚类。我们利用小鼠遗传学方法研究了 Isl 类 LIM 同源结构域蛋白在运动神经元多样化过程中的作用。所有脊髓运动神经元亚型最初都同时表达 Isl1 和 Isl2，但 Isl2 会被内脏运动神经元迅速下调。缺乏 Isl2 功能的小鼠胚胎在胸段运动神经元的迁移和轴突投射方面表现出缺陷，这似乎反映了从内脏运动神经元特征到躯体运动神经元特征的细胞自主转变。减少或消除 Isl1 和 Isl2 活性的其他基因突变会导致内脏运动神经元生成出现更明显的缺陷，并侵蚀躯体运动神经元特征。因此，新生成的运动神经元中高 Isl 表达和活性的早期阶段允许发育中的脊髓内的内脏和躯体运动神经元亚型多样化。
