Inactivation of Hedgehog signal transduction in adult astrocytes results in region-specific blood–brain barrier defects
Hui Wang, Zhiyan Xu, Ziyue Xia, Michael S. Rallo, Andrew J. Duffy, Michael P. Matise
Abstract
Significance Several signaling pathways have been implicated in regulating blood–brain/spinal cord barrier (BBB) properties in the adult mammalian central nervous system (CNS). However, it has become clear that the role of the Sonic hedgehog pathway has not been accurately defined. The current work addresses this issue by demonstrating that the pathway is required in protoplasmic astrocytes to maintain specific BBB characteristics in select regions of the CNS. In contrast to prior studies, we find that astrocytic, and not endothelial cell, Hedgehog signal transduction is required to maintain BBB properties through an effect on transcytosis but not paracellular diffusion. Our discovery raises the possibility that targeted inhibition of the pathway to achieve transient BBB permeability could be exploited for therapeutic purposes.