Abstract 256: Rbp-j Controls the Fate of the Kidney Vasculature
Proper assembly of the renal vasculature is essential for post-natal life, and alterations to the renal vasculature are at the root of many types of cardiovascular disease. However, the mechanisms underlying the establishment, assembly and maintenance of the renal blood vessels are poorly understood. We have identified a population of renal stromal cells (marked by their expression of the transcription factor Foxd1) that differentiate to form the mural cells of the kidney arterial tree (excluding endothelial cells) and the glomerular mesangium. We previously demonstrated that RBP-J, the final transcriptional effector of the Notch signaling pathway, controls the phenotype of renin cells which are also derived from the Foxd1 lineage. We therefore hypothesized that RBP-J regulates the differentiation of stromal cells into the mural cells of the kidney arterioles. To answer this question, we deleted RBP-J in the metanephric stromal precursor cells, and found that mutant mice displayed striking kidney abnormalities in early life. Staining for vascular markers showed a significant decrease in the number of arteries and arterioles. Vessel walls were thinner due to a decrease in both the size and number of smooth muscle cells. We also noted a near absence of renin cells, supporting our earlier findings regarding the key role of RBP-J in establishing the differentiated renin cell endowment. These findings were accompanied by delayed nephrogenesis and other renal abnormalities including tubular dilation. In addition, mutant kidneys lacked Foxd1-lineage cells within the glomeruli, resulting in a depletion of mesangial cells and glomerular aneurysms. Thus, we conclude that RBP-J in Foxd1+ stromal cells plays a key role in the development of the kidney vasculature, and regulates the fate of cells that compose the arterial tree and the glomerular tuft.
- © 2012 by American Heart Association, Inc.