Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning.
Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning.
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DOI：
10.1371/journal.pone.0088400
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sims-Lucas S
中科院分区：
文献类型：
--
作者：
Hum S;Rymer C;Schaefer C;Bushnell D;Sims-Lucas S
肾基质是位于皮质的胚胎细胞群，为发育中的肾脏提供结构框架和内皮祖细胞来源。肾基质在正常肾脏发育中的确切作用尚未明确。然而，之前的研究表明，肾基质特异性基因 Foxd1 的基因缺失会导致严重的肾脏畸形，证实了基质在正常肾脏发育中的重要性。本研究通过消融 Foxd1 衍生的基质细胞本身并观察剩余细胞群的反应，进一步研究肾基质的作用。 Foxd1cre（肾基质特异性）小鼠与白喉毒素小鼠（DTA）杂交，特异性诱导基质细胞凋亡。胚胎第 13.5-18.5 天的肾脏组织学检查显示缺乏基质组织、肾脏结构错误以及发育不良和/或融合的马蹄肾。肾单位祖细胞、脉管系统、输尿管上皮、分化的肾单位祖细胞和血管支持细胞的免疫荧光染色显示，突变体具有增厚的肾单位祖细胞帽、缺乏肾单位祖细胞的皮质区域、异常的血管图案和增厚、输尿管分支缺陷以及分化的肾单位结构迁移到髓质中。 Foxd1基因敲除引起的肾脏畸形与Foxd1DTA小鼠模型之间的相似性揭示了Foxd1在介导和维持肾基质功能完整性方面的重要性。
The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5–18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma.
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DOI：
10.1152/ajprenal.1996.270.5.f886
发表时间：
1996-05-01
影响因子：
4.2
作者：
Hyink, DP;Tucker, DC;Abrahamson, DR
通讯作者：
Abrahamson, DR
DOI：
10.1152/ajprenal.2001.281.2.f345
发表时间：
2001-08-01
影响因子：
4.2
作者：
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通讯作者：
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影响因子：
25
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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