The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development.
The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development.
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DOI：
10.1038/ki.2010.553
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发表时间：
2011-05
影响因子：
19.6
通讯作者：
Salant DJ
中科院分区：
文献类型：
--
作者：
Bonegio RG;Beck LH;Kahlon RK;Lu W;Salant DJ
为了确定哪些肾单位片段需要Notch信号用于发育，我们在后肾间充质的肾发生祖细胞（NP）中有条件地删除了Rbpj，Rbpj是典型Notch信号传导所需的转录因子。视黄酸受体-β2（Rarb 2）启动子有效地将Cre重组酶（Cre）活性引导至这些祖细胞。小鼠中Rbpj的条件性敲除（Rarb 2Cre +/Rbpjf/−）导致严重的肾发育不全，如肾单位数量减少70-95%和管状囊肿的发展所示。为了跟踪Rarb 2Cre表达后NP的命运，我们用膜相关增强型绿色荧光蛋白（GFP）标记它们。在TomatoGFP+/Rarb 2Cre+对照小鼠中，NPs分化成除集合管外的所有肾单位节段的上皮。在TomatoGFP+/Rarb 2Cre +/Rbpjf/−条件性基因敲除小鼠中，NP发育成足细胞或远端肾小管上皮细胞，表明间质向上皮细胞转化或这些肾单位片段的特化不需要经典Notch信号。相反，在这些小鼠中发育的少数近端小管和相关囊肿源自5-10%的未能表达Cre的NP，因此具有完整的Notch信号传导。因此，我们的命运定位研究确定了Notch信号传导对肾发生的深远影响是由于近端而不是远端小管或足细胞的特化。
To determine which nephron segments require Notch signals for development, we conditionally deleted Rbpj, a transcription factor required for canonical Notch signaling, in nephrogenic progenitors (NPs) of the metanephric mesenchyme. The retinoic acid receptor-β2 (Rarb2) promoter efficiently directed Cre-recombinase (Cre) activity to these progenitors. Conditional knockout of Rbpj in mice (Rarb2Cre+/Rbpjf/−) caused severe renal hypoplasia, as indicated by a 70–95% reduction in nephron number and the development of tubular cysts. To track the fate of NPs following Rarb2Cre expression, we labeled them with membrane-associated enhanced green fluorescent protein (GFP). In TomatoGFP+/Rarb2Cre+ control mice, NPs differentiated into epithelia of all nephron segments, except into collecting ducts. In TomatoGFP+/Rarb2Cre+/Rbpjf/−conditional knockout mice, NPs developed into podocytes or distal tubular epithelia, indicating that canonical Notch signals were not required for mesenchymal-to-epithelial transition or for the specification of these nephron segments. Conversely, the few proximal tubules and associated cysts that developed in these mice were derived from the 5–10% of NPs that had failed to express Cre and, therefore, had intact Notch signaling. Thus, our fate mapping studies establish that the profound effect of Notch signaling on nephrogenesis is due to the specification of proximal but not distal tubules or podocytes.
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影响因子：
11.8
作者：
Carroll, TJ;Park, JS;McMahon, AP
通讯作者：
McMahon, AP
影响因子：
29
作者：
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作者：
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作者：
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DOI：
10.1152/ajprenal.00451.2009
发表时间：
2010-01-01
影响因子：
4.2
作者：
Gupta, Sandeep;Li, Shunan;Rosenberg, Mark
通讯作者：
Rosenberg, Mark