Development and Differentiation of Blood Vessels in the Central Nervous System
The central nervous system (CNS) develops from a pseudostratified ectodermal epithelium containing neuroblasts and glioblasts. Other constituents (microglia, blood vessels) are of mesodermal origin and successively invade the neuroectoderm. Using chick-quail chimeras it is possible to study the interaction between neuroectodermal and mesodermal cells. Vascular endothelial cells start invading the CNS of birds at about day 3.5 of development. They originate from the paraxial mesoderm of the head and the trunk. Thereafter, smooth muscle cells migrate along the endothelial routes. Neuroectodermal cells secrete vascular endothelial growth factor (VEGF), which is a highly specific angiogenic and chemoattractive factor. Angioblast and endothelial cells in the paraxial mesoderm are characterized by the expression of VEGF-receptor-2. Except for the choroid plexus, VEGF and VEGF receptors are not expressed in the adult brain. The organ-typical differentiation of endothelial cells in the CNS depends on interactions with local neuroectodermal cells. Development of blood-brain barrier characteristics are obviously due to inductive signals from astrocytes. In contrast, the epithelial cells of the choroid plexus induce development of highly permeable, fenestrated capillaries. Constitutive expression of VEGF and its receptors in the choroid plexus (and the kidney glomeruli) may serve as the basis for high permeability. VEGF has been shown to increase vascular permeability in a highly potent manner.
KeywordsVascular Endothelial Growth Factor Neural Tube Vascular Endothelial Growth Factor Receptor Choroid Plexus Paraxial Mesoderm
Unable to display preview. Download preview PDF.
- Brightman MW (1967) Intracerebral movements of proteins injected into the blood and cerebrospinal fluid. Anat Ree 157: 219Google Scholar
- Ehrlich P (1885) Das Sauerstoff-Bedürfnis des Organismus. Eine farbenanalytische Studie. Habilitationsschrift. A. Hirschwald, BerlinGoogle Scholar
- Feder N, Reese TS, Brightman MW (1969) Microperoxidase, a new tracer of low molecular weight. A study of the interstitial compartements of the mouse brain. J Cell Biol 43: 35a-36aGoogle Scholar
- Goldmann EE (1913) Vitalfarbung am Zentralnervensystem. Abh Preuss Akad. Wiss Phys-Math 1: 1–60Google Scholar
- Lewandowsky M (1900) Zur Lehre von der Cerebrospinalflüssigkeit. Z Klin Med 40: 480–494Google Scholar
- Saunders NR (1992) Ontogenic development of brain barrier mechanisms. In: Bradbury MWB (ed)Handbook of experimental pharmacology. Springer, Berlin Heidelberg New York, pp 327–369Google Scholar
- Wilting J (1988) Ultrastrukturelle und funktionelle Untersuchungen der Entwicklung des Plexus choroideus bei Vogelchimären. Dissertationsarbeit, Ruhr-Universität BochumGoogle Scholar
- Wilting J, Birkenhäger R, Eichmann A, Kurz H, Martiny-Baron G, Marme D, McCarthy JEG, Christ B, Weich HA (1996) VEGF121 induces proliferation of vascular endothelial cells and expression of flk-1 without affecting lymphatic vessels of the chorioallantoic membrane. Dev Biol 176: 76–85PubMedCrossRefGoogle Scholar