Zhang Pili, Bennoun Myriam, Gogard Cécile, Bossard Pascale, Leclerc Isabelle, Kahn Axel, Vasseur-Cognet Mireille
Institut Cochin, IFR 116, INSERM U567, Département de Génétique, Développement et Physiopathologies Moléculaires, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
Mech Dev. 2002 Nov;119(1):109-14. doi: 10.1016/s0925-4773(02)00286-1.
In mammals, the COUP-TF-family consisting of two structurally related proteins, COUP-TFI and COUP-TFII belongs to the orphan member of the steroid/thyroid hormone receptor superfamily. In an attempt to gain insights into the role of COUP-TFII, we examined developmental expression pattern of the mouse COUP-TFII focusing our studies on endoderm-derived tissues, pancreas and liver in particular. Independent lines of transgenic mice expressing Escherichia coli beta-galactosidase driven by the COUP-TFII promoter were generated. Embryonic expression of the beta-gal protein at day 9 of gestation was detected in the notochord, the ventral neural tube and, interestingly, in the gut endoderm, a site where COUP-TFII has not been detected previously. Between 9.5 and 11.5 dpc, beta-gal expression pattern that was established earlier persisted and sections revealed a staining of the common atrial chamber of the heart. At 15.5 dpc, beta-gal activity was found in all endoderm-derived tissues. We found that COUP-TFII mRNA and protein were present in fetal and adult hepatocytes. Finally, COUP-TFII expression was detected in pancreas, as judged by co-expression of the beta-gal in some of the glucagon and PDX1 positive-cells at 12.5 dpc and co-expression with insulin positive-cells at 15.5 dpc. In adult pancreas, COUP-TFII protein was present in the endocrine islet cells.
在哺乳动物中,由两种结构相关蛋白COUP-TFI和COUP-TFII组成的COUP-TF家族属于类固醇/甲状腺激素受体超家族的孤儿成员。为了深入了解COUP-TFII的作用,我们研究了小鼠COUP-TFII的发育表达模式,重点关注内胚层衍生组织,特别是胰腺和肝脏。我们构建了由COUP-TFII启动子驱动表达大肠杆菌β-半乳糖苷酶的转基因小鼠独立品系。在妊娠第9天,在脊索、腹侧神经管中检测到β-半乳糖蛋白的胚胎表达,有趣的是,在肠内胚层中也检测到了该蛋白,而此前从未在该部位检测到COUP-TFII。在胚胎发育9.5至11.5天期间,早期建立的β-半乳糖表达模式持续存在,切片显示心脏的共同心房腔有染色。在胚胎发育15.5天时,在所有内胚层衍生组织中均发现了β-半乳糖活性。我们发现胎儿和成年肝细胞中存在COUP-TFII mRNA和蛋白。最后,通过在胚胎发育12.5天时一些胰高血糖素和PDX1阳性细胞中β-半乳糖的共表达以及在胚胎发育15.5天时与胰岛素阳性细胞的共表达判断,在胰腺中检测到了COUP-TFII的表达。在成年胰腺中,内分泌胰岛细胞中存在COUP-TFII蛋白。