The earliest metanephric arteriolar progenitors and their role in kidney vascular development

The development of the kidney arterioles is poorly understood. Mature arterioles contain several functionally and morphologically distinct cell types, including smooth muscle, endothelial, and juxtaglomerular cells, and they are surrounded by interconnected pericytes, fibroblasts, and other interstitial cells. We have shown that the embryonic kidney possesses all of the necessary precursors for the development of the renal arterial tree, and those precursors assemble in situ to form the kidney arterioles. However, the identity of those precursors was unclear. Within the embryonic kidney, several putative progenitors marked by the expression of either the winged-forkhead transcription factor 1 (Foxd1+ progenitor), the aspartyl-protease renin (Ren+ progenitor), and/or hemangioblasts (Scl+ progenitor) are likely to differentiate and endow most of the cells of the renal arterial tree. However, the lineage relationships and the role of these distinct progenitors in renal vascular morphogenesis have not been delineated. We, therefore, designed a series of experiments to ascertain the hierarchical lineage relationships between Foxd1+ and Ren+ progenitors and the role of these two precursors in the morphogenesis and patterning of the renal arterial tree. Results show that 1) Foxd1+ cells are the precursors for all the mural cells (renin cells, smooth muscle cells, perivascular fibroblasts, and pericytes) of the renal arterial tree and glomerular mesangium, and 2) Foxd1 per se directs the origin, number, orientation, and cellular composition of the renal vessels.