Moritz K M, Wintour E M, Black M J, Bertram J F, Caruana G
School of Biomedical Sciences, University of Queensland, St Lucia, Australia.
Adv Anat Embryol Cell Biol. 2008;196:1-78. doi: 10.1007/978-3-540-77768-7.
There are many reasons why it is timely to review the development of the mammalian kidney. Perhaps the most important of these is the increasing amount of evidence to demonstrate that factors which impinge on/alter the normal developmental processes of this organ can have lifelong consequences for the health of the adult. The'Developmental Origins of Health and Adult Disease' (DOHaD) hypothesis, proposes that changes in the environment during the development of an organ or system, can have permanent deleterious effects leading to increased risk of cardiovascular and/or metabolic disease. The permanent metanephric kidney has been shown to be very vulnerable to such influences with many factors shown to alter both the permanent structure and the level of expression of important functional genes. Thus it is important to understand the precise timing of kidney development in terms of both structure and the genes involved at each stage. Such knowledge has been gained by significant advances in technology, which allow quantification of the number of nephrons by unbiased stereology, detections of both levels and site of gene expression,'knock-out' and knock-in' of genes in animal (mainly mouse) models and by the ability to examine nephron development, in real time, in culture systems.
现在是时候回顾哺乳动物肾脏的发育情况了,原因有很多。其中最重要的或许是,越来越多的证据表明,影响/改变该器官正常发育过程的因素可能会对成年个体的健康产生终身影响。“健康与成人疾病的发育起源”(DOHaD)假说提出,器官或系统发育过程中的环境变化可能会产生永久性有害影响,导致心血管疾病和/或代谢疾病风险增加。已证明永久性后肾极易受到此类影响,许多因素会改变其永久性结构以及重要功能基因的表达水平。因此,从结构和每个阶段所涉及的基因方面了解肾脏发育的确切时间很重要。通过技术的重大进步已经获得了此类知识,这些技术能够通过无偏立体学对肾单位数量进行量化、检测基因表达水平和位点、在动物(主要是小鼠)模型中对基因进行“敲除”和“敲入”,以及能够在培养系统中实时检查肾单位发育情况。