Zoologisches Institut, Abteilung für Zell- und Neurobiologie, Karlsruhe Institute of Technology (KIT), Haid und Neu-Strasse 9, Karlsruhe, Germany.
Glycobiology. 2012 Feb;22(2):196-209. doi: 10.1093/glycob/cwr129. Epub 2011 Sep 2.
Polysialic acid (polySia) is mainly described as a glycan modification of the neural cell adhesion molecule NCAM1. PolySia-NCAM1 has multiple functions during the development of vertebrate nervous systems including axon extension and fasciculation. Phylogenetic analyses reveal the presence of two related gene clusters, NCAM1 and NCAM2, in tetrapods and fishes. Within the ncam1 cluster, teleost fishes express ncam1a (ncam) and ncam1b (pcam) as duplicated paralogs which arose from a second round of ray-finned fish-specific genome duplication. Tetrapods, in contrast, express a single NCAM1 gene. Using the zebrafish model, we identify Ncam1b as a novel major carrier of polySia in the nervous system. PolySia-Ncam1a is expressed predominantly in rostral regions of the developing nervous system, whereas polySia-Ncam1b prevails caudally. We show that ncam1a and ncam1b have different expression domains which only partially overlap. Furthermore, Ncam1a and Ncam1b and their polySia modifications serve different functions in axon guidance. Formation of the posterior commissure at the forebrain/midbrain junction requires polySia-Ncam1a on the axons for proper fasciculation, whereas Ncam1b, expressed by midbrain cell bodies, serves as an instructive guidance cue for the dorso-medially directed growth of axons. Spinal motor axons, on the other hand, depend on axonally expressed Ncam1b for correct growth toward their target region. Collectively, these findings suggest that the genome duplication in the teleost lineage has provided the basis for a functional diversification of polySia carriers in the nervous system.
聚唾液酸（polySia）主要被描述为神经细胞粘附分子 NCAM1 的糖基修饰物。聚唾液酸-NCAM1 在脊椎动物神经系统的发育过程中具有多种功能，包括轴突延伸和聚集。系统发育分析表明，四足动物和鱼类中存在两个相关的基因簇，NCAM1 和 NCAM2。在 ncam1 簇中，硬骨鱼类表达 ncam1a（ncam）和 ncam1b（pcam）作为复制的旁系同源物，它们是由第二轮射线鳍鱼特异性基因组复制产生的。相比之下，四足动物只表达单个 NCAM1 基因。我们使用斑马鱼模型，鉴定出 Ncam1b 是神经系统中聚唾液酸的一种新的主要载体。聚唾液酸-Ncam1a 主要在发育中神经系统的前颅区域表达，而聚唾液酸-Ncam1b 则在前部表达。我们表明，ncam1a 和 ncam1b 具有不同的表达域，仅部分重叠。此外，Ncam1a 和 Ncam1b 及其聚唾液酸修饰在轴突导向中具有不同的功能。前脑/中脑交界处的后连合的形成需要轴突上的聚唾液酸-Ncam1a 进行适当的聚集，而中脑细胞体表达的 Ncam1b 则作为轴突向背内侧生长的指导信号。另一方面，脊髓运动轴突依赖于轴突表达的 Ncam1b 来正确地向其靶区生长。总的来说，这些发现表明，硬骨鱼类谱系中的基因组复制为神经系统中聚唾液酸载体的功能多样化提供了基础。
