Pfeffer P L, Gerster T, Lun K, Brand M, Busslinger M
Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Development. 1998 Aug;125(16):3063-74. doi: 10.1242/dev.125.16.3063.
The mammalian Pax2, Pax5 and Pax8 genes code for highly related transcription factors, which play important roles in embryonic development and organogenesis. Here we report the characterization of all members of the zebrafish Pax2/5/8 family. These genes have arisen by duplications before or at the onset of vertebrate evolution. Due to an additional genome amplification in the fish lineage, the zebrafish contains two Pax2 genes, the previously known Pax[b] gene (here renamed as Pax2.1) and a novel Pax2.2 gene. The zebrafish Pax2.1 gene most closely resembles the mammalian Pax2 gene in its expression pattern, as it is transcribed first in the midbrain-hindbrain boundary region, then in the optic stalk, otic system, pronephros and nephric ducts, and lastly in specific interneurons of the hindbrain and spinal cord. Pax2.2 differs from Pax2.1 by the absence of expression in the nephric system and by a delayed onset of transcription in other Pax2.1 expession domains. Pax8 is also expressed in the same domains as Pax2.1, but its transcription is already initiated during gastrulation in the primordia of the otic placode and pronephric anlage, thus identifying Pax8 as the earliest developmental marker of these structures. The zebrafish Pax5 gene, in contrast to its mouse orthologue, is transcribed in the otic system in addition to its prominent expression at the midbrain-hindbrain boundary. The no isthmus (noi) mutation is known to inactivate the Pax2.1 gene, thereby affecting the development of the midbrain-hindbrain boundary region, pronephric system, optic stalk and otic region. Although the different members of the Pax2/5/8 family may potentially compensate for the loss of Pax2.1 function, we demonstrate here that only the expression of the Pax2.2 gene remains unaffected in noi mutant embryos. The expression of Pax5 and Pax8 is either not initiated at the midbrain-hindbrain boundary or is later not maintained in other expression domains. Consequently, the noi mutation of zebrafish is equivalent to combined inactivation of the mouse Pax2 and Pax5 genes with regard to the loss of midbrain-hindbrain boundary development.
哺乳动物的Pax2、Pax5和Pax8基因编码高度相关的转录因子，这些转录因子在胚胎发育和器官形成中发挥着重要作用。在此，我们报告斑马鱼Pax2/5/8家族所有成员的特征。这些基因是在脊椎动物进化之前或开始时通过基因复制产生的。由于鱼类谱系中额外的基因组扩增，斑马鱼含有两个Pax2基因，即先前已知的Pax[b]基因（此处重新命名为Pax2.1）和一个新的Pax2.2基因。斑马鱼Pax2.1基因在表达模式上与哺乳动物Pax2基因最为相似，因为它首先在中脑-后脑边界区域转录，然后在视柄、耳系统、前肾和肾管中转录，最后在后脑和脊髓的特定中间神经元中转录。Pax2.2与Pax2.1的不同之处在于其在前肾系统中不表达，且在其他Pax2.1表达结构域中的转录起始延迟。Pax8也在与Pax2.1相同的结构域中表达，但其转录在原肠胚形成期间就在耳基板和前肾原基中开始，因此将Pax8确定为这些结构最早的发育标志物。与小鼠同源物相比，斑马鱼Pax5基因除了在中脑-后脑边界有显著表达外，还在耳系统中转录。已知无峡部（noi）突变会使Pax2.1基因失活，从而影响中脑-后脑边界区域、前肾系统、视柄和耳区域的发育。尽管Pax2/5/8家族的不同成员可能潜在地补偿Pax2.1功能的丧失，但我们在此证明，在noi突变胚胎中只有Pax2.2基因的表达不受影响。Pax5和Pax8的表达要么在中脑-后脑边界未起始，要么在其他表达结构域中随后未维持。因此，就中脑-后脑边界发育的丧失而言，斑马鱼的noi突变等同于小鼠Pax2和Pax5基因的联合失活。
