Volume EM revealed stepwise development of the glomerular capillary system through sprouting and Intussusceptive...

The glomerular capillary system is essential for efficient glomerular filtration; however, the morphogenetic processes underlying its development remain incompletely understood. In the present study, we employed two volume EM modalities-array tomography and FIB-SEM tomography-to perform 3D reconstruction of the glomerular capillary system at successive developmental stages in neonatal rats. The results revealed that glomerular capillary development proceeds through four morphologically distinct phases: primitive glomerular capillaries, initial capillary loops, maturing capillary loops, and fully matured capillary loops. Importantly, the glomerular capillary system was found to be established through the combined action of sprouting and intussusceptive angiogenesis. Sprouting angiogenesis was particularly prominent during the formation of primitive glomerular capillaries and initial capillary loops, whereas intussusceptive angiogenesis continued from the S-shaped body stage onward. Furthermore, mesangial cell processes were observed traversing transcapillary pillars and anchoring to the glomerular basement membrane, suggesting an active role for mesangial cells in capillary splitting. These findings provide the first comprehensive ultrastructural description of glomerular capillary development and offer a morphological framework for investigating glomerular capillary anomalies under pathological conditions.