The study investigates the role of pericytes (PCs) in regulating endothelial cell (EC) proliferation, survival, migration, differentiation, and vascular branching during brain angiogenesis. Using PDGF-B- and PDGFR-β-deficient mice as models, the researchers found that the absence of PCs does not affect microvessel density, length, or branching but leads to endothelial hyperplasia, increased capillary diameter, abnormal EC shape and ultrastructure, altered distribution of junctional proteins, and increased transendothelial permeability. These changes were observed from embryonic day (E) 11.5 and persisted throughout development. From E 13.5, upregulation of vascular endothelial growth factor-A (VEGF-A) and other genes responsive to metabolic stress was detected, suggesting systemic metabolic consequences. The increased VEGF-A levels correlated with vascular abnormalities in the placenta and dilation of the heart. The findings indicate that PCs are crucial for maintaining EC number and morphology, and their absence can lead to vascular dysfunction and edema formation in late gestation.The study investigates the role of pericytes (PCs) in regulating endothelial cell (EC) proliferation, survival, migration, differentiation, and vascular branching during brain angiogenesis. Using PDGF-B- and PDGFR-β-deficient mice as models, the researchers found that the absence of PCs does not affect microvessel density, length, or branching but leads to endothelial hyperplasia, increased capillary diameter, abnormal EC shape and ultrastructure, altered distribution of junctional proteins, and increased transendothelial permeability. These changes were observed from embryonic day (E) 11.5 and persisted throughout development. From E 13.5, upregulation of vascular endothelial growth factor-A (VEGF-A) and other genes responsive to metabolic stress was detected, suggesting systemic metabolic consequences. The increased VEGF-A levels correlated with vascular abnormalities in the placenta and dilation of the heart. The findings indicate that PCs are crucial for maintaining EC number and morphology, and their absence can lead to vascular dysfunction and edema formation in late gestation.