Molven A, Njølstad P R, Fjose A
Laboratory of Biotechnology, HIB, University of Bergen, Norway.
EMBO J. 1991 Apr;10(4):799-807. doi: 10.1002/j.1460-2075.1991.tb08012.x.
The Wnt-1 (int-1) gene was originally identified as an oncogene, but its normal function is in embryogenesis. The gene is the vertebrate homologue of the Drosophila segment polarity gene wingless, and encodes a secretory protein. In mouse embryos, Wnt-1 expression is necessary for proper development of the midbrain and anterior hindbrain. Here we describe the molecular cloning and primary structure of the zebrafish Wnt-1 gene (denoted wnt-1). Comparison with its mouse homologue reveals that both the genomic organization of wnt-1 and the amino acid sequence of the corresponding gene product have been extensively conserved during vertebrate evolution. Moreover, there is probably at least one Wnt-1-related sequence in the zebrafish genome. In zebrafish embryos, wnt-1 is expressed during differentiation of the neural tube. In situ hybridization analysis reveals that the transcripts are confined to the dorsal surfaces of the midbrain, hindbrain and spinal cord, and to lateral cells at the midbrain-hindbrain junction. Thus, the pattern of wnt-1 expression in the developing central nervous system of zebrafish is virtually identical to that seen in mouse embryos. Unexpectedly, despite the striking similarities of Wnt-1 structure and expression in fish and higher vertebrates, we could not identify sequences of obvious homology outside the coding regions, neither in the promoter nor in the introns.
Wnt-1(int-1)基因最初被鉴定为一种癌基因,但其正常功能是在胚胎发生过程中发挥作用。该基因是果蝇节段极性基因无翅基因(wingless)的脊椎动物同源物,编码一种分泌蛋白。在小鼠胚胎中,Wnt-1的表达对于中脑和前脑后部的正常发育是必需的。在此,我们描述了斑马鱼Wnt-1基因(命名为wnt-1)的分子克隆和一级结构。与小鼠同源物的比较表明,在脊椎动物进化过程中,wnt-1的基因组组织以及相应基因产物的氨基酸序列都得到了广泛的保守。此外,斑马鱼基因组中可能至少存在一个与Wnt-1相关的序列。在斑马鱼胚胎中,wnt-1在神经管分化过程中表达。原位杂交分析显示,转录本局限于中脑、后脑和脊髓的背表面以及中脑-后脑交界处的外侧细胞。因此,斑马鱼发育中的中枢神经系统中wnt-1的表达模式与小鼠胚胎中所见的模式几乎相同。出乎意料的是,尽管鱼类和高等脊椎动物中Wnt-1的结构和表达有显著相似之处,但我们在编码区之外,无论是启动子还是内含子中,都未能鉴定出明显的同源序列。