Abstract：
Whereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal\'s growth, maturation processes, the addition of new neurons, body movements, and aging. The Caenorhabditis elegans protein SAX-7, homologous to the vertebrate L1 protein family of neural adhesion molecules, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function of sax-7 in neuronal maintenance, we generated a null allele and sax-7S-isoform-specific alleles. We find that the null sax-7(qv30) is, in some contexts, more severe than previously described mutant alleles and that the loss of sax-7S largely phenocopies the null, consistent with sax-7S being the key isoform in neuronal maintenance. Using a sfGFP::SAX-7S knock-in, we observe sax-7S to be predominantly expressed across the nervous system, from embryogenesis to adulthood. Yet, its role in maintaining neuronal organization is ensured by postdevelopmentally acting SAX-7S, as larval transgenic sax-7S(+) expression alone is sufficient to profoundly rescue the null mutants\' neuronal maintenance defects. Moreover, the majority of the protein SAX-7 appears to be cleaved, and we show that these cleaved SAX-7S fragments together, not individually, can fully support neuronal maintenance. These findings contribute to our understanding of the role of the conserved protein SAX-7/L1CAM in long-term neuronal maintenance and may help decipher processes that go awry in some neurodegenerative conditions.
摘要：
尽管显著的进步已经发现了驱动神经系统组装的机制，负责神经系统结构的终身维护的过程仍然知之甚少。在胚胎发生期间建立之后，神经元结构是维持在整个生命面对动物的成长，成熟过程，增加新的神经元，身体运动,和衰老。秀丽隐杆线虫蛋白SAX-7，与脊椎动物L1蛋白家族的神经粘附分子同源，是在成功的初始胚胎发育后维持神经元神经节和束的组织所必需的。解剖sax-7在神经元维持中的功能，我们产生了无效等位基因和sax-7S同工型特异性等位基因。我们发现空sax-7(qv30)是，在某些情况下,比以前描述的突变等位基因更严重，并且萨克斯-7S的丢失在很大程度上表现了无效，与sax-7S是神经元维持的关键同工型一致。使用sfGFP::SAX-7S敲入，我们观察到sax-7S主要在神经系统中表达，从胚胎发育到成年。然而，它在维持神经元组织中的作用是通过后发育作用的SAX-7S来确保的，作为幼虫转基因sax-7S（）表达本身就足以深刻地挽救无效突变体\'神经元维持缺陷。此外，大部分的SAX-7蛋白似乎被切割，我们证明了这些切割的SAX-7S片段在一起，不是单独的,可以完全支持神经元的维持。这些发现有助于我们了解保守蛋白SAX-7/L1CAM在长期神经元维持中的作用，并可能有助于破译某些神经退行性疾病中出错的过程。
