Glomerulogenesis and the role of endothelium

Earlier works of the glomerulogenesis described morphological steps and protein expression during in-vivo and in-vitro kidney development. Recent technologies using cell-specific or conditional knock-out mice for several factors provide important knowledge about cross-talk signaling among resident cells as local events. Based on the recent advancement, this review revisits comprehensive morphological development of the glomerulus.

Interactions of presumptive podocyte vascular endothelial growth factor with vascular endothelial growth factor-2 on angioblasts initiate glomerular vascularization. In induced pluripotent stem cells or organoid-derived nephron formation, the lack of endothelium and mesangial cells under differentiated podocytes suggests the presence of another unknown mechanism for glomerular neovascularization. Mesangial cell migration is prerequisite for glomerular looping by interaction of endothelial platelet-derived grothe factor beta and mesangial platelet-derived growth factor receptor beta and requires the coreceptor neuropilin1. Development of the filtration barrier is promoted by cross-talk among resident cells and may need shear stress. The components of the glomerular basement membrane change during glomerulogenesis, and endothelium and podocytes produce laminin and type IV collagen α1 and α2, whereas type IV collagen α3, α4, α5 is derived only from podocytes.

Glomerulogenesis progresses by dynamic cellular migration/differentiation induced by cross-talk signaling in resident cells. Glomerular vasculogenesis and subsequent capillary development provide insight into glomerular regeneration and remodeling for medical application.