Cessation of renal morphogenesis in mice
Cessation of renal morphogenesis in mice
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DOI：
10.1016/j.ydbio.2007.08.021
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发表时间：
2007-10-15
影响因子：
2.7
通讯作者：
Patterson, Larry T.
中科院分区：
文献类型：
--
作者：
Hartman, Heather A.;Lai, Hsiao L.;Patterson, Larry T.
肾脏的发育经历了输尿管芽分枝和肾单位的形成。通过输尿管芽尖和周围间充质之间的相互感应作用和反馈，周期开始并维持。了解周期是如何结束的很重要，因为它控制着肾单位的数量。在小鼠肾发生结束的时期，我们检查了控制分支和肾发生的结构域的形态、基因表达和功能。我们发现，继续分支所需的肾源性间质在出生后第三天就消失了。这与在没有细胞凋亡的情况下新肾单位形成速度加快有关。同时，输尿管芽支末端失去了壶腹的典型外观和WNT11的表达，这与无盖间充质的情况一致。令人惊讶的是，Wnt9b基因的表达仍在继续，这是间充质诱导所必需的基因。然后我们对出生后第三天的芽分枝顶端进行了测试，结果表明它在培养中保持了促进后肾间充质存活和诱导肾发生的能力。这些结果表明，导致分枝、形态发生和肾脏发生周期中断的一系列事件始于其转化为肾单位所导致的间质丧失。(C)2007 Elsevier Inc.保留所有权利。
The kidney develops by cycles of ureteric bud branching and nephron formation. The cycles begin and are sustained by reciprocal inductive interactions and feedback between ureteric bud tips and the surrounding mesenchyme. Understanding how the cycles end is important because it controls nephron number. During the period when nephrogenesis ends in mice, we examined the morphology, gene expression, and function of the domains that control branching and nephrogenesis. We found that the nephrogenic mesenchyme, which is required for continued branching, was gone by the third postnatal day. This was associated with an accelerated rate of new nephron formation in the absence of apoptosis. At the same time, the tips of the ureteric bud branches lost the typical appearance of an ampulla and lost Wnt11 expression, consistent with the absence of the capping mesenchyme. Surprisingly, expression of Wnt9b, a gene necessary for mesenchyme induction, continued. We then tested the postnatal day three bud branch tip and showed that it maintained its ability both to promote survival of metanephric mesenchyme and to induce nephrogenesis in culture. These results suggest that the sequence of events leading to disruption of the cycle of branching morphogenesis and nephrogenesis began with the loss of mesenchyme that resulted from its conversion into nephrons. (C) 2007 Elsevier Inc. All rights reserved.