Characterization of mesonephric development and regeneration using transgenic zebrafish

Characterization of mesonephric development and regeneration using transgenic zebrafish
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DOI:
10.1152/ajprenal.00394.2010
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发表时间:
2010-11-01
影响因子:
4.2
通讯作者:
Hildebrandt, Friedhelm
Hildebrandt, Friedhelm
中科院分区:
医学2区
文献类型:
--
作者:
Zhou, Weibin;Boucher, Rudrick C.;Hildebrandt, Friedhelm

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周伟,周文杰,周伟。转基因斑马鱼中肾发育及再生的研究进展。[J] .中国生物医学工程学报,2016,31(4):557 - 557。首次发表于2010年9月1日;doi: 10.1152 / ajprenal.00394.2010。斑马鱼是研究肾脏的有价值的脊椎动物模型。以往的研究大多集中在斑马鱼的原肾上,它只有两个肾细胞,结构比成年鱼的中肾和哺乳动物的后肾简单。为了评估斑马鱼系统对肾脏发育和再生的更复杂的研究,我们研究了成年斑马鱼中肾的发育和损伤后再生。利用两种转基因斑马鱼株系(wt1b::GFP和pod::NTR-mCherry),研究了个体中肾肾细胞的发育阶段和中肾发生的时空格局。我们发现斑马鱼的中肾形成贯穿其整个生命周期,在幼鱼时期有一个快速的生长期,而在成年期则有一个较慢的生长期,因此幼鱼和成年鱼的总肾单位数量与体重呈线性相关。庆大霉素诱导的肾损伤后,斑马鱼中肾可以经历中肾肾元的新生再生,这一过程被称为新肾发生。我们发现,早在损伤后48小时,中肾间质中单个分散的细胞就诱导了wt1b的表达。这些表达wt1b的细胞在损伤后72-96小时形成聚集体,进而形成肾单位。这表明wt1b可能是肾祖细胞的早期标记物。再生新肾发生的同步性表明,这一过程可能对肾元发育的研究有用。
Zhou W, Boucher RC, Bollig F, Englert C, Hildebrandt F. Characterization of mesonephric development and regeneration using transgenic zebrafish. Am J Physiol Renal Physiol 299: F1040-F1047, 2010. First published September 1, 2010; doi:10.1152/ajprenal.00394.2010.-The zebrafish is a valuable vertebrate model for kidney research. The majority of previous studies focused on the zebrafish pronephros, which comprises only two nephrons and is structurally simpler than the mesonephros of adult fish and the metanephros of mammals. To evaluate the zebrafish system for more complex studies of kidney development and regeneration, we investigated the development and postinjury regeneration of the mesonephros in adult zebrafish. Utilizing two transgenic zebrafish lines (wt1b::GFP and pod::NTR-mCherry), we characterized the developmental stages of individual mesonephric nephrons and the temporal-spatial pattern of mesonephrogenesis. We found that mesonephrogenesis continues throughout the life of zebrafish, with a rapid growth phase during the juvenile period and a slower phase in adulthood such that the total nephron number of juvenile and adult fish linearly correlates with body mass. Following gentamicin-induced renal injury, the zebrafish mesonephros can undergo de novo regeneration of mesonephric nephrons, a process known as neonephrogenesis. We found that wt1b expression was induced in individually dispersed cells in the mesonephric interstitium as early as 48 h following injury. These wt1b-expressing cells formed aggregates by 72-96 h following injury which proceeded to form nephrons. This suggests that wt1b may serve as an early marker of fated renal progenitor cells. The synchronous nature of regenerative neonephrogenesis suggests that this process may be useful for studies of nephron development.