Development of the renal vasculature

Abstract

The kidney vasculature has a unique and complex architecture that is central for the kidney to exert its multiple and essential physiological functions with the ultimate goal of maintaining homeostasis. An appropriate development and coordinated assembly of the different vascular cell types and their association with the corresponding nephrons is crucial for the generation of a functioning kidney. In this review we provide an overview of the renal vascular anatomy, histology, and current knowledge of the embryological origin and molecular pathways involved in its development. Understanding the cellular and molecular mechanisms involved in renal vascular development is the first step to advance the field of regenerative medicine.

Keywords: Angiogenesis; Endothelial cells; Fate tracing; Lineage; Mural cells; Vasculogenesis.

Figure 1

Microdissected renal arterial trees throughout development. Modified from [31].

Figure 2

Developmental origin and lineage relationships of the precursors for the metanephric kidney. Arrows indicate current knowledge and question marks possibilities that require further investigation.

Figure 3

Development of glomerular capillaries in S-shaped glomerulus. [A-C] 50 nm embryonic mouse kidney sections under transmission electron microscopy showing “tip cell” like endothelial cell (EC) (A, squared) with filopodia (B) and red blood cells (RBCs) in the vessel lumen formed by the invading ECs (C) in S-shaped glomeruli. [D] Schematic diagram demonstrating that ECs (in yellow) form vessel lumens with RBCs (in red) in the vascular cleft of an S-shaped glomerulus (in blue). M, mesangial cell. PD, podocyte. PT, proximal tubule. Scale bar: A-C, 5μm. From [175]

Figure 4

Major molecular mechanisms in kidney vascular development. Representation of interactions between the endothelial and mural cells (vascular smooth muscle and renin cells). Within the glomerulus a podocyte and a mesangial cell are represented whereas endothelial cells (which express the same receptors and ligands as the one on the left side) are not depicted for clarity.

Figure 5

Rbpj is required for the proper pattern and formation of the renal arterial tree. Microdissected renal arterial trees from control and Foxd1^Rboj−/− mice showing a marked decrease in arterial and arteriolar branches and duplication of the renal artery (arrowheads) when Rbpj is missing in the progenitors of the renal mural cells.