Emoto Yumi, Wada Hironori, Okamoto Hitoshi, Kudo Akira, Imai Yoshiyuki
Department of Biological Information, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Dev Biol. 2005 Feb 15;278(2):415-27. doi: 10.1016/j.ydbio.2004.11.023.
Retinoic acid (RA) plays a critical role in neural patterning and organogenesis in the vertebrate embryo. Here we characterize a mutant of the zebrafish named giraffe (gir) in which the gene for the RA-degrading enzyme Cyp26a1 is mutated. The gir mutant displayed patterning defects in multiple organs including the common cardinal vein, pectoral fin, tail, hindbrain, and spinal cord. Analyses of molecular markers suggested that the lateral plate mesoderm is posteriorized in the gir mutant, which is likely to cause the defects of the common cardinal vein and pectoral fin. The cyp26a1 expression in the rostral spinal cord was strongly upregulated in the gir mutant, suggesting a strong feedback control of its expression by RA signaling. We also found that the rostral spinal cord territory was expanded at the expense of the hindbrain territory in the gir mutant. Such a phenotype is the opposite of that of the mutant for Raldh2, an enzyme that synthesizes RA. We propose a model in which Cyp26a1 attenuates RA signaling in the prospective rostral spinal cord to limit the expression of hox genes and to determine the hindbrain-spinal cord boundary.
视黄酸（RA）在脊椎动物胚胎的神经模式形成和器官发生中起着关键作用。在此，我们鉴定了一种名为长颈鹿（gir）的斑马鱼突变体，其中视黄酸降解酶Cyp26a1的基因发生了突变。gir突变体在包括总主静脉、胸鳍、尾巴、后脑和脊髓在内的多个器官中表现出模式缺陷。分子标记分析表明，gir突变体中侧板中胚层向后化，这可能导致总主静脉和胸鳍的缺陷。gir突变体中，延髓脊髓中cyp26a1的表达强烈上调，表明视黄酸信号对其表达有强烈的反馈控制。我们还发现，gir突变体中延髓脊髓区域以牺牲后脑区域为代价而扩大。这种表型与合成视黄酸的酶Raldh2的突变体表型相反。我们提出了一个模型，其中Cyp26a1减弱了前脑脊髓中视黄酸信号，以限制hox基因的表达并确定后脑-脊髓边界。
