Gajewski Martin, Elmasri Harun, Girschick Manuel, Sieger Dirk, Winkler Christoph
Universität zu Köln, Institut für Genetik [corrected] Zülpicher Str., 47, 50674 Köln, Germany.
Dev Genes Evol. 2006 Jun;216(6):315-32. doi: 10.1007/s00427-006-0059-6. Epub 2006 Mar 17.
Somitogenesis is the key developmental step, which divides the vertebrate body axis into segmentally repeated structures. It requires an intricate process of pre-patterning, which is driven by an oscillator mechanism consisting of the Delta-Notch pathway and various hairy- and Enhancer of split-related (her) genes. The subset of her genes, which are necessary to set up the segmentation clock, reveal a complex scenario of interactions. To understand which her genes are essential core players in this process, we compared the expression patterns of somitogenesis-relevant her genes in zebrafish and medaka (Oryzias latipes). Most of the respective medaka genes (Ol-her) are duplicated like what has been shown for zebrafish (Dr-her) and pufferfish genes (Fr-her). However, zebrafish genes show some additional copies and significant differences in expression patterns. For the paralogues Dr-her1 and Dr-her11, only one copy exists in the medaka (Ol-her1/11), which combines the expression patterns found for both zebrafish genes. In contrast to Dr-her5, the medaka orthologue appears to play a role in somitogenesis because it is expressed in the presomitic mesoderm (PSM). PSM expression also suggests a role for both Ol-her13 genes, homologues of mouse Hes6 (mHes6), in this process, which would be consistent with a conserved mHes6 homologue gear in the segmentation clock exclusively in lower vertebrates. Members of the mHes5 homologue group seem to be involved in somite formation in all vertebrates (e.g. Dr- and Ol-her12), although different paralogues are additionally recruited in zebrafish (e.g. Dr-her15) and medaka (e.g. Ol-her4). We found that the linkage between duplicates is strongly conserved between pufferfish and medaka and less well conserved in zebrafish. Nevertheless, linkage and orientation of several her duplicates are identical in all three species. Therefore, small-scale duplications must have happened before whole genome duplication occurred in a fish ancestor. Expression of multiple stripes in the intermediate PSM, characteristic for the zebrafish orthologues, is absent in all somitogenesis-related her genes of the medaka. In fact, the expression mode of Ol-her1/11 and Ol-her5 indicates dynamism similar to the hairy clock genes in chicken and mouse. This suggests that Danio rerio shows a rather derived clock mode when compared to other fish species and amniotes or that, alternatively, the clock mode evolved independently in zebrafish, medaka and mouse or chicken.
体节发生是关键的发育步骤，它将脊椎动物的体轴划分为分段重复的结构。这需要一个复杂的预模式形成过程，该过程由一个由Delta-Notch信号通路以及各种毛状和分裂增强子相关（her）基因组成的振荡机制驱动。在建立体节时钟中必需的her基因子集揭示了一个复杂的相互作用情况。为了了解哪些her基因是这个过程中必不可少的核心参与者，我们比较了斑马鱼和青鳉（日本青鳉）中与体节发生相关的her基因的表达模式。大多数相应的青鳉基因（Ol-her）都像斑马鱼（Dr-her）和河豚基因（Fr-her）那样发生了复制。然而，斑马鱼基因显示出一些额外的拷贝以及表达模式上的显著差异。对于旁系同源物Dr-her1和Dr-her11，青鳉中只存在一个拷贝（Ol-her1/11），它结合了在两个斑马鱼基因中发现的表达模式。与Dr-her5不同，青鳉的直系同源物似乎在体节发生中起作用，因为它在前体节中胚层（PSM）中表达。PSM表达也表明两个Ol-her13基因（小鼠Hes6（mHes6）的同源物）在这个过程中起作用，这与仅在低等脊椎动物的体节时钟中存在保守的mHes6同源物机制是一致的。mHes5同源物组的成员似乎在所有脊椎动物的体节形成中都有参与（例如Dr-her和Ol-her1），尽管在斑马鱼（例如Dr-her15）和青鳉（例如Ol-her4）中还额外招募了不同的旁系同源物。我们发现河豚和青鳉中重复基因之间的连锁关系高度保守，而在斑马鱼中保守性较差。然而，几个her重复基因的连锁和方向在所有三个物种中是相同的。因此，小规模的重复必定在鱼类祖先发生全基因组重复之前就已经发生了。青鳉所有与体节发生相关的her基因中都不存在斑马鱼直系同源物特有的中间PSM中的多条带表达。事实上，Ol-her1/11和Ol-her5的表达模式表明其具有与鸡和小鼠中的毛状时钟基因相似的动态性。这表明与其他鱼类物种和羊膜动物相比，斑马鱼显示出一种相当衍生的时钟模式，或者，时钟模式在斑马鱼、青鳉以及小鼠或鸡中是独立进化的。
