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.

Nyckelord

Animals

Basement Membrane

cytology

metabolism

Brain

cytology

metabolism

Cell Differentiation

Female

Forkhead Transcription Factors

genetics

physiology

Gene Expression Profiling

Gene Expression Regulation

Developmental

Gene Library

Glomerular Mesangium

cytology

metabolism

In Situ Hybridization

Integrases

metabolism

Kidney Glomerulus

cytology

physiology

Male

Mice

Mice

Inbred ICR

Mice

Knockout

Nephrons

cytology

metabolism

Oligonucleotide Array Sequence Analysis

Podocytes

cytology

metabolism

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)