pdzrn3是非洲爪蟾原肾形态发生所必需的。

S. Marracci, A. Vangelisti, V. Raffa, M. Andreazzoli, L. Dente
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引用次数: 4

摘要

Pdzrn3是一种具有e3泛素连接酶活性的多结构域蛋白,已被报道在成肌细胞和成骨细胞分化中发挥作用,最近在神经元和内皮细胞发育中也起作用。pdzrn3基因的表达在多种脊椎动物组织中受到发育调控,包括肌肉、神经和血管系统。尽管已经发现人类pdzrn3染色体区域周围的遗传多态性和改变与肾细胞癌和其他肾脏疾病有关,但对其在肾脏发育过程中的表达知之甚少。利用原位杂交技术研究了pdzrn3基因在非洲爪蟾胚胎中的时空表达规律。我们重点研究了原肾的发育,这是胚胎两栖动物的肾脏,功能上类似于人类肾脏最原始的肾脏结构。为了探讨pdzrn3在肾脏形态发生中的作用,我们通过反义morpholino注射进行了功能丧失实验,并使用特异性肾源标记分析了变形体。pdzrn3在体细胞、脑、眼、血岛、心、肝、肾等胚胎组织中均有动态表达。功能丧失实验导致肾原发育的特异性改变。特别是,在早期阶段,pdzrn3耗竭与肾原胶原蛋白的减少有关,后来与小管形成的扰动有关,包括近端小管的变形。救援实验中,斑马鱼pdzrn3同源基因的mRNA与morpholino一起注射,允许肾脏表型的恢复。这些结果强调了pdzrn3表达对正确肾形成的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
pdzrn3 is required for pronephros morphogenesis in Xenopus laevis.
Pdzrn3, a multidomain protein with E3-ubiquitin ligase activity, has been reported to play a role in myoblast and osteoblast differentiation and, more recently, in neuronal and endothelial cell development. The expression of the pdzrn3 gene is developmentally regulated in various vertebrate tissues, including muscular, neural and vascular system. Little is known about its expression during kidney development, although genetic polymorphisms and alterations around the human pdzrn3 chromosomal region have been found to be associated with renal cell carcinomas and other kidney diseases. We investigated the pdzrn3 spatio-temporal expression pattern in Xenopus laevis embryos by in situ hybridization. We focused our study on the development of the pronephros, which is the embryonic amphibian kidney, functionally similar to the most primitive nephric structures of human kidney. To explore the role of pdzrn3 during renal morphogenesis, we performed loss-of-function experiments, through antisense morpholino injections and analysed the morphants using specific pronephric markers. Dynamic pdzrn3 expression was observed in embryonic tissues, such as somites, brain, eye, blood islands, heart, liver and pronephros. Loss of function experiments resulted in specific alterations of pronephros development. In particular, at early stages, pdzrn3 depletion was associated with a reduction of the pronephros anlagen and later, with perturbations of the tubulogenesis, including deformation of the proximal tubules. Rescue experiments, in which mRNA of the zebrafish pdzrn3 orthologue was injected together with the morpholino, allowed recovery of the kidney phenotypes. These results underline the importance of pdzrn3 expression for correct nephrogenesis.
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