Activation of Wnt/β-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation.

The central nervous system (CNS) requires specialized blood vessels to support neural function within specific microenvironments. During neurovascular development, endothelial Wnt/β-catenin signaling is required for BBB development within the brain parenchyma, whereas fenestrated blood vessels that lack BBB properties do not require Wnt/β-catenin signaling. Here, we used zebrafish to further characterize this phenotypic heterogeneity of the CNS vasculature.

IL-1β disrupts the initiation of blood-brain barrier development by inhibiting endothelial Wnt/β-catenin signaling.

During neuroinflammation, the proinflammatory cytokine interleukin-1β (IL-1β) impacts blood-brain barrier (BBB) function by disrupting brain endothelial tight junctions, promoting vascular permeability, and increasing transmigration of immune cells. Here, we examined the effects of Il-1β on the initiation of BBB development. We generated doxycycline-inducible transgenic zebrafish to secrete Il-1β in the CNS.

IL-1β disrupts blood-brain barrier development by inhibiting endothelial Wnt/β-catenin signaling.

During neuroinflammation, the proinflammatory cytokine Interleukin-1β (IL-1β) impacts blood-brain barrier (BBB) function by disrupting brain endothelial tight junctions, promoting vascular permeability, and increasing transmigration of immune cells. Here, we examined the effects of Il-1β on the development of the BBB. We generated a doxycycline-inducible transgenic zebrafish model that drives secretion of Il-1β in the CNS.

Brain endothelial cells acquire blood-brain barrier properties in the absence of Vegf-dependent CNS angiogenesis.

During neurovascular development, brain endothelial cells (BECs) respond to secreted signals from the neuroectoderm that regulate CNS angiogenesis, the formation of new blood vessels in the brain, and barriergenesis, the acquisition of blood-brain barrier (BBB) properties. Wnt/β-catenin signaling and Vegf signaling are both required for CNS angiogenesis; however, the relationship between these pathways is not understood. Furthermore, while Wnt/β-catenin signaling is essential for barriergenesis, the role of Vegf signaling in this vital process remains unknown.

Functional identification of the zebrafish Interleukin-1 receptor in an embryonic model of Il-1β-induced systemic inflammation.

Interleukin-1β (IL-1β) is a potent proinflammatory cytokine that plays a vital role in the innate immune system. To observe the innate immune response , several transgenic zebrafish lines have been developed to model IL-1β-induced inflammation and to visualize immune cell migration and proliferation in real time. However, our understanding of the IL-1β response in zebrafish is limited due to an incomplete genome annotation and a lack of functional data for the cytokine receptors involved in the inflammatory process.