Large-scale identification of genes implicated in kidney glomerulus development and function.
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.
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Minoru
M
Takemoto
Liqun
L
He
Jenny
J
Norlin
Jaakko
J
Patrakka
Zhijie
Z
Xiao
Tatiana
T
Petrova
Cecilia
C
Bondjers
Julia
J
Asp
Elisabet
E
Wallgard
Ying
Y
Sun
Tore
T
Samuelsson
Petter
P
Mostad
Samuel
S
Lundin
Naoyuki
N
Miura
Yoshikazu
Y
Sado
Kari
K
Alitalo
Susan E
SE
Quaggin
Karl
K
Tryggvason
Christer
C
Betsholtz
D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D017403:In Situ Hybridization; D019426:Integrases / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009399:Nephrons / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D050199:Podocytes / Q000166:cytology / Q000378:metabolism
D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein; C045073:Cre recombinase; D019426:Integrases