Pod1 is required in stromal cells for glomerulogenesis

Pod1 is required in stromal cells for glomerulogenesis
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DOI:
10.1002/dvdy.10244
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发表时间:
2003-03-01
影响因子:
2.5
通讯作者:
Quaggin, SE
Quaggin, SE
中科院分区:
生物学3区
文献类型:
--
作者:
Cui, SY;Schwartz, L;Quaggin, SE

文献摘要

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Pod 1(capsulin/epicardin/Tcf 21)是一种碱性螺旋-环-螺旋转录因子,在发育器官(包括肾脏、肺、肠道和心脏)的间充质中高度表达。BMPod 1小鼠出生后不久就因肺部缺乏肺泡和心脏缺陷而死亡。此外,肾脏发育不全,输尿管芽上皮的分支形态发生中断,肾单位数量明显减少,肾小球发生延迟,血管异常。为了进一步剖析Pod 1在肾脏发育过程中的细胞功能,通过聚集空Pod 1胚胎干细胞和普遍表达增强型绿色荧光蛋白(GFP)的小鼠胚胎来产生嵌合小鼠。组织学,免疫组化和原位杂交分析所得到的嵌合后代证明了细胞自主和非细胞自主的作用,在特定的肾细胞系,包括肾小管周间质细胞和周细胞的分化为Pod 1。最引人注目的是,肾小球形成缺陷被野生型基质细胞的存在所拯救,这表明Pod 1在该细胞群中的非细胞自主作用。(C)2003 Wiley-Liss,Inc.
Pod1 (capsulin/epicardin/Tcf21) is a basic-helix-loop-helix transcription factor that is highly expressed in the mesenchyme of developing organs that include the kidney, lung, gut, and heart. Null Pod1 mice are born but die shortly after birth due to a lack of alveoli in the lungs and cardiac defects. In addition, the kidneys are hypoplastic and demonstrate disrupted branching morphogenesis of the ureteric bud epithelium, a marked reduction in the number of nephrons, a delay in glomerulogenesis, and blood vessel abnormalities. To further dissect the cellular function of Pod1 during kidney development, chimeric mice were generated through aggregations of null Pod1 embryonic stem cells and murine embryos ubiquitously expressing enhanced green fluorescent protein (GFP). Histologic, immunohistochemical, and in situ hybridization analysis of the resulting chimeric offspring demonstrated both cell autonomous and non-cell autonomous roles for Pod1 in the differentiation of specific renal cell lineages that include peritubular interstitial cells and pericytes. Most strikingly, the glomerulogenesis defect was rescued by the presence of wild-type stromal cells, suggesting a non-cell autonomous role for Pod1 in this cell population. (C) 2003 Wiley-Liss, Inc.