Fukushige Tetsunari, Goszczynski Barbara, Yan Jie, McGhee James D
Department of Biochemistry and Molecular Biology, Genes and Development Research Group, University of Calgary Faculty of Medicine, Room 2205 Health Sciences Centre, 3330 Hospital Drive, N.W., Calgary, Alberta, Canada T2N 4N1.
Dev Biol. 2005 Mar 15;279(2):446-61. doi: 10.1016/j.ydbio.2004.12.012.
We have previously described an acid phosphatase enzyme, PHO-1, present at the lumenal surface of all but the anterior six cells of the Caenorhabditis elegans intestine. In the present paper, we identify the pho-1 structural gene, which encodes a histidine acid phosphatase showing highest similarity to human prostatic acid phosphatase. The pho-1 5'-flanking DNA is capable of directing reporter gene expression that is both gut specific, correctly timed and correctly "patterned", that is, not expressed in the gut anterior. Furthermore, this anterior-posterior patterning of pho-1 expression responds to the C. elegans Wnt pathway as if pho-1 is repressed (directly or indirectly) by high levels of the HMG effector protein POP-1. Transgenic analysis of the pho-1 promoter shows that gut expression is critically dependent on a single WGATAR site. The gut-specific GATA factor ELT-2 binds to this site in vitro and removal of ELT-2 from the embryo destroys expression of the pho-1 reporter. Thus, all our results indicate that pho-1 is a direct downstream target of ELT-2. Finally, the pho-1 loss-of-function mutation shows an interesting and unexpected phenotype for a somatically-expressed hydrolytic enzyme: loss of pho-1 causes arrest of the majority of embryos but this lethality is a maternal effect. We suggest that pho-1 is required by the maternal intestine to assimilate some nutrient or cleavage product that is subsequently provided to the next generation of embryos.
我们之前描述过一种酸性磷酸酶PHO-1,它存在于秀丽隐杆线虫肠道除前六个细胞外的所有细胞的腔表面。在本文中,我们鉴定出了pho-1结构基因,该基因编码一种组氨酸酸性磷酸酶,与人类前列腺酸性磷酸酶具有最高的相似性。pho-1的5'侧翼DNA能够指导报告基因的表达,这种表达具有肠道特异性、正确的时间调控和正确的“模式”,即在肠道前部不表达。此外,pho-1表达的这种前后模式对秀丽隐杆线虫的Wnt信号通路有反应,就好像pho-1受到高水平的HMG效应蛋白POP-1的抑制(直接或间接)。对pho-1启动子的转基因分析表明,肠道表达严重依赖于一个WGATAR位点。肠道特异性GATA因子ELT-2在体外与该位点结合,从胚胎中去除ELT-2会破坏pho-1报告基因的表达。因此,我们所有的结果都表明pho-1是ELT-2的直接下游靶点。最后,pho-1功能缺失突变对于一种体细胞表达的水解酶表现出一种有趣且意想不到的表型:pho-1的缺失导致大多数胚胎发育停滞,但这种致死性是一种母体效应。我们认为母体肠道需要pho-1来吸收一些营养物质或裂解产物,随后这些物质会提供给下一代胚胎。