Hartman Heather A, Lai Hsiao L, Patterson Larry T
Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Dev Biol. 2007 Oct 15;310(2):379-87. doi: 10.1016/j.ydbio.2007.08.021. Epub 2007 Aug 16.
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.
肾脏通过输尿管芽分支和肾单位形成的循环过程发育。这些循环始于输尿管芽尖与周围间充质之间的相互诱导相互作用和反馈，并以此维持。了解这些循环如何结束很重要，因为它控制着肾单位数量。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区域的形态、基因表达和功能。我们发现，持续分支所必需的肾发生间充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率加快有关。与此同时，输尿管芽分支的尖端失去了壶腹的典型外观，并失去了Wnt11表达，这与覆盖间充质的缺失一致。令人惊讶的是，间充质诱导所必需的基因Wnt9b的表达仍在继续。然后我们测试了出生后第三天的芽分支尖端，结果表明它在培养中既保持了促进后肾间充质存活的能力，又保持了诱导肾发生的能力。这些结果表明，导致分支形态发生和肾发生循环中断的一系列事件始于间充质转化为肾单位而导致的间充质丧失。
