Pericytes are required for blood–brain barrier integrity during embryogenesis

By R. Daneman, Lu Zhou, Amanuel A. Kebede, B. Barres. Nature, 2010

1,980 citations recorded by the source corpus.

Vascular endothelial cells in the central nervous system (CNS) form a barrier that restricts the movement of molecules and ions between the blood and the brain. This blood–brain barrier (BBB) is crucial to ensure proper neuronal function and protect the CNS from injury and disease. Transplantation studies have demonstrated that the BBB is not intrinsic to the endothelial cells, but is induced by interactions with the neural cells. Owing to the close spatial relationship between astrocytes and endothelial cells, it has been hypothesized that astrocytes induce this critical barrier postnatally, but the timing of BBB formation has been controversial. Here we demonstrate that the barrier is formed during embryogenesis as endothelial cells invade the CNS and pericytes are recruited to the nascent vessels, over a week before astrocyte generation. Analysing mice with null and hypomorphic alleles of Pdgfrb, which have defects in pericyte generation, we demonstrate that pericytes are necessary for the formation of the BBB, and that absolute pericyte coverage determines relative vascular permeability. We demonstrate that pericytes regulate functional aspects of the BBB, including the formation of tight junctions and vesicle trafficking in CNS endothelial cells. Pericytes do not induce BBB-specific gene expression in CNS endothelial cells, but inhibit the expression of molecules that increase vascular permeability and CNS immune cell infiltration. These data indicate that pericyte–endothelial cell interactions are critical to regulate the BBB during development, and disruption of these interactions may lead to BBB dysfunction and neuroinflammation during CNS injury and disease.

Subfields: Cell Biology, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/c2a56b4ee85ffe91ac614398452c609518b5c7e4

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Citations in the corpus

Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. (2015, neutral): “Most lower ties during development (Daneman et al., 2010; Obermeier et al., 2013).”
The blood–brain barrier in systemic infection and inflammation (2021, background): “The first is the maintenance of BBB integrity by inhibition of transcytosis and by induction of endothelial cell expression of tight junction proteins [59, 60] and major facilitator domain-containing protein 2A (MFSD2a), a docosahexaenoic acid transporter [61].”
The blood-brain barrier in Alzheimer's disease (2017, positive): “Pericytes are recruited to the nascent vessels during embryogenesis more than a week before astrocytes emerge, and they are necessary for the formation of the BBB (Daneman et al., 2010).”
The blood-brain barrier. (2015, background): “Comparative microarray analysis has identified that effectors of Wnt/b-catenin signaling, including Lef1, Apcdd1, and tnfrsf19, are enriched CNS ECs compared to ECs in peripheral organs (Daneman et al. 2009, 2010a).”
Central nervous system pericytes in health and disease (2011, background): “Pericytes and the neurovascular unit Pericytes are uniquely positioned within the NVU, serving as vital integrators, coordinators and effectors of neurovascular functions including regulation of blood brain barrier (BBB) permeabilit”
The blood–brain barrier in health and disease: Important unanswered questions (2020, background): “…low paracellular permeability in peripheral vessels as in the CNS. Expression data suggest that the answer might lie in the CNS-specific enrichment of certain cytoplasmic adaptors (e.g., JACOP,MPP7) and tricellular TJ molecules such as LSR and MARVELD2 (Daneman et al., 2010a; Sohet et al., 2015).”
Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. (2019, background): “Pericyte number is positively correlated with BBB tightness (41).”