microRNA-184 distribution and consequences on glial septate junctions and the blood-brain barrier

Abstract

Cellular permeability barriers restrict the diffusion of solutes, pathogens, and cells across tissues. In Drosophila melanogaster, septate and tricellular junctions create permeability barriers in epithelia and the blood-brain barrier in glia. In vitro, and in vivo studies in the epithelia of the Drosophila wing imaginal discs identified microRNA-184 (miR-184) as a potential regulator of a subset of pleated septate and tricellular junction proteins. However, which tissues express miR-184, and the consequences of miR-184 expression on the blood-brain barrier has not been examined. Using a miR-184 sensor, we found that miR-184 is absent in tissues with pleated septate junctions but is present in tissues with smooth septate junctions. When expressed in the subperineurial glia that form the blood-brain barrier, miR-184 resulted in the loss of targeted septate junction proteins, a compromised blood-brain barrier, decreased locomotion, and lethality. Interestingly, qRT-PCR analysis revealed that miR-184 expression did not alter mRNA levels of targeted genes. Conversely, expression of miR-184 led to an increase in the mRNA and expression of the non-target Nervana2 protein. Thus, mRNA-184 can regulate multiple pleated septate junction proteins either directly through loss of translation or indirectly by disruption of the septate junction domain.