Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment
Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment
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DOI：
10.1016/j.ydbio.2009.05.578
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发表时间：
2009-08-15
影响因子：
2.7
通讯作者：
Little, Melissa H.
中科院分区：
文献类型：
--
作者：
Georgas, Kylie;Rumballe, Bree;Little, Melissa H.
虽然已知肾单位的形成是由帽状间充质向上皮转化形成肾小囊（RV）而启动的，但肾单位随后的模式形成以及与肾脏输尿管成分融合形成通畅连续的泌尿小管的过程尚未完全阐明。我们利用双重原位杂交（SISH）/免疫组织化学（IHC）技术，揭示了肾小囊阶段肾单位内Notch、骨形态发生蛋白（BMP）和Wnt通路成分明显的远端/近端模式。有丝分裂和细胞周期蛋白D1表达的定量分析表明，远端肾小囊中的细胞增殖更高，这反映了近端和远端细胞群不同的发育程序。少数肾小囊基因也在肾单位的早期连接段表达。双重原位杂交/免疫组织化学结合连续切片免疫荧光和三维重建显示，晚期肾小囊和相邻输尿管顶端之间通过一个涉及输尿管上皮基底膜缺失以及表达肾小囊标志物的细胞插入输尿管顶端的过程发生融合。利用Six2 - eGFPCre×R26R - 1acZ小鼠，我们证明这些细胞来源于帽状间充质，而非输尿管上皮。因此，在晚期肾小囊阶段，肾单位的模式形成和通畅性均明显。（C）2009爱思唯尔公司。保留所有权利。
While nephron formation is known to be initiated by a mesenchyme-to-epithelial transition of the cap mesenchyme to form a renal vesicle (RV), the subsequent patterning of the nephron and fusion with the ureteric component of the kidney to form a patent contiguous uriniferous tubule has not been fully characterized. Using dual section in situ hybridization (SISH)/immunohistochemistry (IHC) we have revealed distinct distal/proximal patterning of Notch, BMP and Wnt pathway components within the RV stage nephron. Quantitation of mitoses and Cyclin D1 expression indicated that cell proliferation was higher in the distal RV, reflecting the differential developmental programs of the proximal and distal populations. A small number of RV genes were also expressed in the early connecting segment of the nephron. Dual ISH/IHC combined with serial section immunofluorescence and 3D reconstruction revealed that fusion occurs between the late RV and adjacent ureteric tip via a process that involves loss of the intervening ureteric epithelial basement membrane and insertion of cells expressing RV markers into the ureteric tip. Using Six2-eGFPCre x R26R-1acZ mice, we demonstrate that these cells are derived from the cap mesenchyme and not the ureteric epithelium. Hence, both nephron patterning and patency are evident at the late renal vesicle stage. (C) 2009 Elsevier Inc. All rights reserved.