Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden.
Dev Biol. 2013 Sep 15;381(2):377-88. doi: 10.1016/j.ydbio.2013.06.026. Epub 2013 Jul 9.
The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50-60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions.
淀粉样前体蛋白(APP)是一种跨膜蛋白,主要因其与阿尔茨海默病的关联而被认识。由于 APP 家族中的基因冗余,APP 的生理功能仍未完全被理解。在这项研究中,我们使用斑马鱼来研究斑马鱼 APP 同源物 appb 在发育过程中的生理功能。我们发现 appb 在脊髓中的有丝分裂后神经元中表达。appb 的敲低导致自发卷曲增加和触摸诱导的活动延长的行为表型。这些胚胎中的脊髓运动神经元表现出缺陷的形成和轴突生长模式。Appb 的减少也导致神经肌肉接头的前突触和后突触的模式缺陷和密度改变。总之,我们的数据表明,斑马鱼功能性运动的发育依赖于 Appb 在运动神经元和神经肌肉接头的模式形成中的关键作用。