Large-scale identification of genes implicated in kidney glomerulus development and function
Large-scale identification of genes implicated in kidney glomerulus development and function
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DOI：
10.1038/sj.emboj.7601014
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发表时间：
2006-03-08
期刊：
影响因子：
11.4
通讯作者：
Betsholtz, C
中科院分区：
文献类型：
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作者：
Takemoto, M;He, LQ;Betsholtz, C
为了进一步了解肾小球的发育、功能和疾病，我们建立了小鼠肾小球不同发育阶段的cDNA文库，并对其进行了大规模测序，得到了6053个不同基因的目录。对纯化的肾小球、非肾小球肾组织、facs分选的足细胞和脑毛细血管的一系列标记靶点进行测序和杂交，鉴定出300多个富集肾小球细胞的转录本，其中一些转录本通过原位杂交进一步亚定位到足细胞、系膜细胞和肾小球旁细胞。对于最早发现的足细胞标记Foxc2，我们使用敲除小鼠来分析该蛋白在肾小球发育过程中的作用。我们发现Foxc2控制一组不同的足细胞基因的表达，这些基因参与足细胞分化和肾小球基底膜成熟。原发性足细胞缺陷也引起肾小球血管细胞的异常分化和组织。我们推测，对本研究中发现的其他新的肾小球富集转录本的研究将为肾小球的发育和疾病的病理机制提供新的见解。
To advance our understanding of development, function and diseases in the kidney glomerulus, we have established and large-scale sequenced cDNA libraries from mouse glomeruli at different stages of development, resulting in a catalogue of 6053 different genes. The glomerular cDNA clones were arrayed and hybridized against a series of labeled targets from isolated glomeruli, non-glomerular kidney tissue, FACS-sorted podocytes and brain capillaries, which identified over 300 glomerular cell-enriched transcripts, some of which were further sublocalized to podocytes, mesangial cells and juxtaglomerular cells by in situ hybridization. For the earliest podocyte marker identified, Foxc2, knockout mice were used to analyze the role of this protein during glomerular development. We show that Foxc2 controls the expression of a distinct set of podocyte genes involved in podocyte differentiation and glomerular basement membrane maturation. The primary podocyte defects also cause abnormal differentiation and organization of the glomerular vascular cells. We surmise that studies on the other novel glomerulus-enriched transcripts identified in this study will provide new insight into glomerular development and pathomechanisms of disease.