Global Quantification of Tissue Dynamics in the Developing Mouse Kidney
Global Quantification of Tissue Dynamics in the Developing Mouse Kidney
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DOI：
10.1016/j.devcel.2014.02.017
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发表时间：
2014-04-28
影响因子：
11.8
通讯作者：
Little, Melissa H.
中科院分区：
文献类型：
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作者：
Short, Kieran M.;Combes, Alexander N.;Little, Melissa H.
尽管相同大小的肾脏在出生时肾单位数量可能会变化10倍，但由于缺乏定义肾脏发育的定量参数，发现调节这种变化的因素一直受到阻碍。在这里，我们报告了一个全面的，定量的，多尺度的分析哺乳动物肾脏发育中，我们测量细胞数量的变化，室体积，细胞动力学在整个器官发生，专注于两个关键的肾祖细胞群体：输尿管上皮和帽间充质。在这样做时，我们描述了一个不连续的发展计划，这些关键的细胞群体之间的相互作用发生在一个以前不受重视的结构刻板的器官架构的动态变化。我们还说明了应用这种方法检测一个微妙的突变表型。肾脏形态发生的基线计划提供了一个评估遗传和环境发育扰动的框架，并将作为其他器官分析的金标准。
Although kidneys of equal size can vary 10-fold in nephron number at birth, discovering what regulates such variation has been hampered by a lack of quantitative parameters defining kidney development. Here we report a comprehensive, quantitative, multiscale analysis of mammalian kidney development in which we measure changes in cell number, compartment volumes, and cellular dynamics across the entirety of organogenesis, focusing on two key nephrogenic progenitor populations: the ureteric epithelium and the cap mesenchyme. In doing so, we describe a discontinuous developmental program governed by dynamic changes in interactions between these key cellular populations occurring within a previously unappreciated structurally stereotypic organ architecture. We also illustrate the application of this approach to the detection of a subtle mutant phenotype. This baseline program of kidney morphogenesis provides a framework for assessing genetic and environmental developmental perturbation and will serve as a gold standard for the analysis of other organs.