Large-scale identification of genes implicated in kidney glomerulus development and function.
Artikel i vetenskaplig tidskrift, 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

cytology

Basement Membrane

metabolism

Knockout

cytology

Forkhead Transcription Factors

Integrases

physiology

Mice

Glomerular Mesangium

Animals

Kidney Glomerulus

Gene Library

physiology

Female

Mice

metabolism

Nephrons

Developmental

cytology

metabolism

Gene Expression Regulation

genetics

metabolism

metabolism

Inbred ICR

Oligonucleotide Array Sequence Analysis

Podocytes

Cell Differentiation

Gene Expression Profiling

cytology

Mice

cytology

Brain

Male

cytology

In Situ Hybridization

Författare

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

Göteborgs universitet

Julia Asp

Göteborgs universitet

Elisabet Wallgard

Karolinska Institutet

Ying Sun

Karolinska Institutet

Tore Samuelsson

Göteborgs universitet

Petter Mostad

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Samuel B Lundin

Göteborgs universitet

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 1160-74

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1038/sj.emboj.7601014