Combes Alexander N
Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
Nephrology (Carlton). 2015 May;20(5):312-4. doi: 10.1111/nep.12407.
Kidney growth is dependent on functional interactions between mesenchymal nephron progenitors, the ureteric epithelium and surrounding stroma, which together make up the nephrogenic niche. Signalling between these populations regulates nephron progenitor maintenance, branching morphogenesis and nephron induction. Nephron endowment is sensitive to changes in the size of the nephron progenitor pool and to decreases in factors that promote branching morphogenesis. However, determining the morphogenic consequences of these disruptions in vivo has been challenging as quantitating kidney morphogenesis is hampered by the size, opacity and three-dimensional complexity of the tissue. The recent application of whole mount immunofluorescence and tissue clearing, coupled with multiscale imaging and quantitative analysis, has begun to give insights into the dynamics of kidney formation. This review focuses on how the quantitative nature of this approach has enabled mathematical modelling of cell cycle lengths, growth rates, cell number and branching rates and is advancing our understanding of kidney organogenesis.
肾脏的生长依赖于间充质肾单位祖细胞、输尿管上皮和周围基质之间的功能相互作用,它们共同构成了肾发生龛。这些细胞群体之间的信号传导调节肾单位祖细胞的维持、分支形态发生和肾单位诱导。肾单位数量对肾单位祖细胞池大小的变化以及促进分支形态发生的因子减少很敏感。然而,在体内确定这些破坏的形态发生后果具有挑战性,因为肾脏形态发生的定量受到组织大小、不透明度和三维复杂性的阻碍。全组织免疫荧光和组织透明化技术的最新应用,结合多尺度成像和定量分析,已开始为肾脏形成的动力学提供见解。本综述重点关注这种方法的定量性质如何实现对细胞周期长度、生长速率、细胞数量和分支速率的数学建模,并正在推动我们对肾脏器官发生的理解。