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Large‐scale identification of genes implicated in kidney glomerulus development and function
Author(s) -
Takemoto Minoru,
He Liqun,
Norlin Jenny,
Patrakka Jaakko,
Xiao Zhijie,
Petrova Tatiana,
Bondjers Cecilia,
Asp Julia,
Wallgard Elisabet,
Sun Ying,
Samuelsson Tore,
Mostad Petter,
Lundin Samuel,
Miura Naoyuki,
Sado Yoshikazu,
Alitalo Kari,
Quaggin Susan E,
Tryggvason Karl,
Betsholtz Christer
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601014
Subject(s) - library science , computer science
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.