Large-scale identification of genes implicated in kidney glomerulus development and function.
Journal article, 2006
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.
metabolism
Oligonucleotide Array Sequence Analysis
Developmental
Gene Library
metabolism
Animals
Gene Expression Regulation
In Situ Hybridization
metabolism
Nephrons
cytology
Inbred ICR
cytology
Mice
metabolism
metabolism
Basement Membrane
Female
physiology
Mice
Kidney Glomerulus
physiology
metabolism
Cell Differentiation
cytology
Integrases
cytology
Glomerular Mesangium
Forkhead Transcription Factors
Male
Knockout
Gene Expression Profiling
genetics
cytology
Podocytes
cytology
Brain
Mice
Author
Minoru Takemoto
Karolinska Institutet
Liqun He
Karolinska Institutet
Jenny Norlin
Karolinska Institutet
Jaakko Patrakka
Karolinska Institutet
Zhijie Xiao
Karolinska Institutet
Tatiana Petrova
Helsingin Yliopisto
Cecilia Bondjers
University of Gothenburg
Julia Asp
University of Gothenburg
Elisabet Wallgard
Karolinska Institutet
Ying Sun
Karolinska Institutet
Tore Samuelsson
University of Gothenburg
Petter Mostad
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Samuel B Lundin
University of Gothenburg
Naoyuki Miura
Hamamatsu University School of Medicine
Yoshikazu Sado
Shigei Medical Research Institute
Kari Alitalo
Helsingin Yliopisto
Susan E Quaggin
University of Toronto
Karl Tryggvason
Karolinska Institutet
Christer Betsholtz
Karolinska Institutet
EMBO Journal
0261-4189 (ISSN) 1460-2075 (eISSN)
Vol. 25 5 1160-74Subject Categories (SSIF 2011)
MEDICAL AND HEALTH SCIENCES
DOI
10.1038/sj.emboj.7601014