Article
- The EMBO Journal (2006) 25, 1160 - 1174
- doi:10.1038/sj.emboj.7601014
Published online: 23 February 2006
Subject Categories:
Large-scale identification of genes implicated in kidney glomerulus development and function
Minoru Takemoto1, Liqun He1, Jenny Norlin1, Jaakko Patrakka1, Zhijie Xiao1, Tatiana Petrova2, Cecilia Bondjers3, Julia Asp4, Elisabet Wallgard1, Ying Sun1, Tore Samuelsson3, Petter Mostad5, Samuel Lundin6, Naoyuki Miura7, Yoshikazu Sado8, Kari Alitalo9, Susan E Quaggin10, Karl Tryggvason1 and Christer Betsholtz1,11
- Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Molecular Cancer Biology Program, Biomedicum, University of Helsinki, Helsinki, Finland
- Department of Medical Biochemistry, Göteborg University, Göteborg, Sweden
- Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Göteborg, Sweden
- Department of Mathematical Statistics, Chalmers University of Technology, Göteborg, Sweden
- Department of Medical Microbiology and Immunology, Göteborg University, Göteborg, Sweden
- Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan
- Division of Immunology, Shigei Medical Research Institute, Okayama, Japan
- Molecular/Cancer Biology Laboratory, Biomedicum, University of Helsinki, Helsinki, Finland
- Department of Maternal and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Correspondence to:
Christer Betsholtz, Laboratory of Vascular Biology, Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, House A3, Plan 4, Scheeles vag 2, 171 77 Stockholm, Sweden. Tel.: +46 8 5248 7960; Fax: +46 8 313445; E-mail: christer.betsholtz@ki.se
Received 16 November 2005; Accepted 30 January 2006
Abstract
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.
Keywords:
- Foxc2,
- kidney glomerulus,
- mesangial cells,
- podocyte,
- transcription profiling
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