Developmental Biology

Making a Tight Seal

Science Signaling  25 Nov 2008:
Vol. 1, Issue 47, pp. ec400
DOI: 10.1126/scisignal.147ec400

Permeability of the endothelial lining of blood vessels in the central nervous system (CNS) is more restricted than it is in blood vessels in other parts of the body. This creates a highly selective blood-brain barrier that protects the CNS from blood-borne toxins and pathogens, but little is known about how the blood-brain barrier is formed (see the Perspective by Lammert). Stenman et al. report that Wnt7a and Wnt7b are produced in the neuroepithelium, the embryonic tissue from which the CNS is derived, during its vascularization and that at least one of these ligands must be present for proper vascularization of the CNS. Animals that lacked both Wnt7a and Wnt7b function in the neuroepithelium exhibited a hemorrhaging phenotype in the CNS, and genetic experiments indicated that the canonical Wnt signaling pathway effector β-catenin was required in the vascular endothelium, but not in the neuroepithelium, for proper vascularization. The glucose transporter GLUT1, which is initially expressed in the neuroepithelium, becomes restricted to and enriched in the vascular epithelium as the blood-brain barrier is formed, and this switch in GLUT1 expression required Wnt7 and Wnt7b. These results imply a model in which Wnt7a and Wnt7b produced by the neuroepithelium activate a canonical Wnt signaling pathway in the invading vascular endothelium, signaling through which is required for characteristically high expression of glucose transporter GLUT1 in the blood-brain barrier. These results may provide a starting point for determining how the blood-brain barrier is formed and therefore how its permeability may be developmentally compromised or clinically manipulated.

J. M. Stenman, J. Rajagopal, T. J. Carroll, M. Ishibashi, J. McMahon, A. P. McMahon, Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature. Science 322, 1247–1250 (2008). [Abstract] [Full Text]

E. Lammert, Brain Wnts for blood vessels. Science 322, 1195–1196 (2008). [Summary] [Full Text]