Editors' ChoiceNeuroscience

Hedgehogs Man the Gate

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Science Signaling  03 Jan 2012:
Vol. 5, Issue 205, pp. ec6
DOI: 10.1126/scisignal.2002807

The blood-brain barrier (BBB) is composed of tightly bound endothelial cells and perivascular astrocytes and keeps potentially harmful cells and blood-borne molecules away from the brain. In neurological diseases such as multiple sclerosis, the BBB is breached, and inflammatory mediators and cells gain access to the brain and contribute to disease pathology. Alvarez et al. (see the Perspective by Engelhardt) now demonstrate that Sonic hedgehog (Shh) signaling promotes BBB integrity. Pharmacological inhibition of Shh signaling or genetic ablation of Shh signaling in endothelial cells increased BBB permeability in mice. In a mouse model of multiple sclerosis, blockade of Shh signaling increased disease severity. Inflammation promoted Shh signaling, and expression of Shh signaling mediators was elevated in multiple sclerosis lesions.

J. I. Alvarez, A. Dodelet-Devillers, H. Kebir, I. Ifergan, P. J. Fabre, S. Terouz, M. Sabbagh, K. Wosik, L. Bourbonnière, M. Bernard, J. van Horssen, H. E. de Vries, F. Charron, A. Prat, The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science 334, 1727–1731 (2011). [Abstract] [Full Text]

B. Engelhardt, Blood-brain barrier differentiation. Science 334, 1652–1653 (2011). [Abstract] [Full Text]

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