Table 1.
Establishment of the blood-brain barrier: signaling pathways and molecules
| Murine Timeline | Pathway | Cell to Cell Interaction | BBB Targets | Reference Nos. |
|---|---|---|---|---|
| Angiogenesis and vascular remodeling | ||||
| E10 to postnatal | VEGF-VEGFR/neuropilin1 | Neural epithelial-angioblasts, tip cells, stalk cells | Ras, PI3K, Src, p38MAPK (intracellular signaling) | 243 |
| E10 to postnatal | TGF-β- neuropilin1 | Neural epithelial-angioblasts, tip cells, stalk cells | SMAD, CDC42 (intracellular signaling) | 603 |
| E10 to postnatal | Notch-DLL4 | Tip cells, stalk cells | NICD, Jagged (intracellular signaling) | 65 |
| E10 to postnatal | Wnt, Norrin, Frizzled, Grp124, Reck, LRP5/LRP6 | Neural progenitors-endothelial | β-Catenin (nuclear translocation) | 609 |
| Barriergenesis and BBB maturation | ||||
| E10 to E16 | Wnt, Norrin, Frizzled, Grp124, Reck, β-catenin, LRP5/LRP6 | Neuron-endothelial | Claudin3 (tight junction) | 350 |
| Plvap (transcellular flow) | ||||
| Laminin, collagen IV | 98 | |||
| Glut1 (transporters) | 542 | |||
| DR6, Troy (receptor) | 557 | |||
| E10 to postnatal | PDGF-BB-Pdgfrβ | Endothelial-pericyte | PI3K, Src, p38MAPK (intracellular signaling) | 553 |
| E10 to postnatal | TGF-β-ALK5 | Endothelial-pericyte | SMAD (intracellular signaling) | 621 |
| E10 to postnatal | Angiopoietin-Tie2 | Pericyte-endothelial | PI3K, Rho, NFκB (intracellular signaling) | 26 |
| E10 to postnatal | Semaphorin-plexin/ neuropilin1 | Neural progenitors-endothelial | VE-cadherin (intercellular junctions) | 338 |
| E10 to postnatal | Netrin-DCC/UNC5 | Endothelial cell autonomous | JAM-A, occluding, claudin-5, ZO-1, α-catenin (intercellular junctions) | 459, 633 |
| E17 to postnatal | SHH, PTCH, SMO, Gli | Astrocyte-endothelial | Occludin, JAM-A, VE-cadherin, claudin-3 and claudin-5 (intercellular junctions) | 12 |
| IL-8, ICAM-1, CCL2 (inflammatory mediator) | ||||
| E17 to postnatal | SSeCKS | Astrocyte-endothelial | ZO-1 | 339 |
| E15 to postnatal | Transporters | Endothelial cell autonomous | Glut1 (transporters) | 622 |
| Mfsd2a (transporters) | 61 | |||
| E15 to postnatal | Junctions | Endothelial-endothelial | Claudin-5 (tight junction) | 425 |
| Lsr (tricellular junction) | 535 | |||
| BBB maintenance | ||||
| Postnatal to adult | apoE- LRP1-CypA-MMP-9 | Astrocyte-pericyte-endothelial | MMP-9 | 59 |
| Postnatal to adult | Interferon-λ-IFNLR1 | Peripheral-BBB | ZO-1, claudin-5 (tight junction) | 337 |
| Postnatal to adult | PDGF-BB-Pdgfrβ | Endothelial-pericyte | PI3K, Src, p38MAPK (intracellular signaling) | 423 |