McWhorter Michelle L, Monani Umrao R, Burghes Arthur H M, Beattie Christine E
Center for Molecular Neurobiology, The Ohio State University, Columbus, OH 43210, USA.
J Cell Biol. 2003 Sep 1;162(5):919-31. doi: 10.1083/jcb.200303168.
Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by a loss of alpha motoneurons in the spinal cord. SMA is caused by low levels of the ubiquitously expressed survival motor neuron (Smn) protein. As it is unclear how low levels of Smn specifically affect motoneurons, we have modeled SMA in zebrafish, a vertebrate model organism with well-characterized motoneuron development. Using antisense morpholinos to reduce Smn levels throughout the entire embryo, we found motor axon-specific pathfinding defects. Reduction of Smn in individual motoneurons revealed that smn is acting cell autonomously. These results show for the first time, in vivo, that Smn functions in motor axon development and suggest that these early developmental defects may lead to subsequent motoneuron loss.
脊髓性肌萎缩症（SMA）是一种常染色体隐性疾病，其特征是脊髓中的α运动神经元丧失。SMA是由普遍表达的生存运动神经元（Smn）蛋白水平低下所致。由于尚不清楚低水平的Smn如何具体影响运动神经元，我们在斑马鱼（一种具有特征明确的运动神经元发育过程的脊椎动物模式生物）中构建了SMA模型。使用反义吗啉代寡核苷酸降低整个胚胎中的Smn水平，我们发现了运动轴突特异性的寻路缺陷。在单个运动神经元中降低Smn水平显示，smn是在细胞自主发挥作用。这些结果首次在体内表明，Smn在运动轴突发育中发挥作用，并提示这些早期发育缺陷可能导致随后的运动神经元丧失。
