Abstract

The blood–brain barrier (BBB) is a cellular structure in the central nervous system (CNS) that restricts the molecular and cellular exchanges. The pathological disruption of BBB has been implicated in a wide spectrum of neurological disorders. Tight junctions (TJs) and transporters possess the central role to achieve the highly integrated mechanism of the BBB to strictly isolate the vertebrate CNS. TJs restrict the distance between adjacent epithelial cells lining the fine capillaries of the brain microvasculature to form a selective physical barrier. On the other hand, ATP binding cassette (ABC) transporters are known to be utilized for chemoprotection that actively expel lipophilic molecules. In spite of accumulating ex vivo models as well studies using rodents, it has still been less well understood how BBB function is established and maintained. In Drosophila, “BBB” and epithelial paracellular barriers are provided by a type of glia, subperineurial glia (SPG), that are connected by septate junctions (SJs) that have functional and molecular similarities to vertebrate TJs. It has also been revealed that Drosophila also conserves the xenobiotic exclusion system which is achieved by fly ABC transporter(s). We thus aimed to address the molecular mechanisms for regulating the BBB functions in vivo using powerful Drosophila genetics. To this end, we have set up a genetic system to perform a large-scale screen to identify novel genes that are involved in the formation and maintenance of the BBB functions. In our system, we have identified several genes that are required for the integrity of paracellular junction.

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