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 C. 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 post-developmentally 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.

中文翻译：

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神经元发育后作用的 SAX-7S/L1CAM 可以作为切割片段来维持秀丽隐杆线虫的神经元结构。

尽管显着的进展已经揭示了驱动神经系统组装的机制，但对神经系统结构终身维持的过程仍然知之甚少。在胚胎发生过程中建立神经元结构后，面对动物的生长、成熟过程、新神经元的添加、身体运动和衰老，神经元结构在整个生命中都保持不变。C. elegans 蛋白 SAX-7 与脊椎动物 L1 蛋白家族的神经粘附分子同源，是在胚胎成功发育后维持神经元神经节和束的组织所必需的。为了剖析 sax-7 在神经元维持中的功能，我们生成了一个无效等位基因和 sax-7S-isoform-specific 等位基因。我们发现空 sax-7(qv30) 在某些情况下是 比先前描述的突变等位基因更严重，并且 sax-7S 的丢失主要是 phenocopies null，这与 sax-7S 是神经元维持中的关键同种型一致。使用 sfGFP::SAX-7S 敲入，我们观察到 sax-7S 主要在整个神经系统中表达，从胚胎发育到成年。然而，其在维持神经元组织中的作用是通过发育后作用的 SAX-7S 来确保的，因为仅幼虫转基因 sax-7S(+) 表达就足以深刻地拯救空突变体的神经元维持缺陷。此外，大多数蛋白质 SAX-7 似乎被切割，我们证明这些切割的 SAX-7S 片段一起，而不是单独，可以完全支持神经元维持。