Analysis of molecular mechanism and cell-cell interactions in the establishment of left-right asymmetry

脊椎动物心脏和肠道器官的左右不对称是在发育过程中产生的。我们调查了Shh、Pitx2和维甲酸参与了这个过程，并认为它们是左撇子的罪魁祸首。特别是，我们从斑马鱼中克隆了Pitx2基因，分析了其表达模式、功能、基因调控以及与维甲酸的相互作用(Tsukui et al.，1999)。另一方面，我们克隆了T-box基因家族中与器官形成和模式形成密切相关的几个成员，以研究它们在左右不对称中的功能。我们分析了它们在斑马鱼胚胎中的表达模式(Yonei-Tamura等人，1999；Tamura等人，1999)，并证实了Tbx5/4在鸡胚胎中的重要作用(Rodriguez-Esteban等人，1999)。我们还启动了一个关于比目鱼和左右不对称的项目。我们检查和评估了视交叉作为左右不对称的一个重要表型，并将其作为左右不对称的指标杆。我们还克隆了几个左右不对称的关键基因片段，包括Pitx2、Fgf8、Noda11和MSx(2)。上述结果发表在一篇综述文章(Tamura et al.，1999)上。

Left-right asymmetry in heart and intestinal organs of vertebrates is produced in the process of their development. We investigated that shh, Pitx2 and retinoic acid are involved in this process, and that they are responsible for the left handedness. In particular, we cloned Pitx2 gene from zebrafish and analyzed its expression pattern, function, gene regulations, and interaction with retinoic acid (Tsukui et al., 1999).On the other hand, we cloned several members of T-box gene family, which are largely involved in organ for mation and patterning, in order to examine their functions on left-right asymmetry. We analyzed their expression patterns in zebrafish embryo (Yonei-Tamura et al., 1999 ; Tamura et al., 1999), and confirmed an important role of Tbx5/4 in chick embryo (Rodriguez-Esteban et al., 1999).We also started a project on flounder and left-right asymmetry. We examined and evaluated the visual chiasma as a significant phenotype of left-right asymmetry, and used as a guidepost of left-right asymmetry. We also cloned several PCR fragments of key genes on left-right asymmetry, includeing Pitx2, fgf8, Noda11, and msx (2) from the flounder.The above results were published in a review article (Tamura et al., 1999).