Cell Biology

Barrier Maintenance

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Science  21 Dec 2012:
Vol. 338, Issue 6114, pp. 1512
DOI: 10.1126/science.338.6114.1512-b

The central nervous system (CNS) and retina are privileged areas of blood vessel growth and function. For example, the specialized vasculature restricts the diffusion of toxic molecules and the entry of pathogens into these regions. Frizzled4, a protein expressed at the surface of vascular endothelial cells (ECs), and its activating ligand Norrin are important for the development of blood vessel networks. Wang et al. now report that in the mouse, Norrin-Frizzled4 signaling is required for early vascular development in the retina and also later in the CNS to maintain vascular integrity. In genetically engineered mice lacking either Norrin or Frizzled4, retinal blood vessel growth was slow, formed irregular, criss-crossed patterns, and failed to create a trilayer architecture. The authors could also visualize leakage of these blood vessels in regions of the brain, spinal cord, olfactory bulb, and retina, and show that Norrin-Frizzled4 signaling is needed for the expression of cell junction proteins. In mice engineered to lack Frizzled4 in only a few percent of the EC population, general vascular organization appeared normal, but was leaky only in regions of blood vessels where Frizzled4 was absent. The loss of either the blood-brain or blood-retina barrier occurs in many disorders, including stroke, diabetes, infections, and eye disease. The Norrin-Frizzled4 signaling pathway may thus be a new therapeutic target.

Cell 151, 1332 (2012).

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