The Drosophila blood-brain barrier: development and function of a glial endothelium

Abstract

The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial (SPG) cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells.

Coupled Sensing of Hunger and Thirst Signals Balances Sugar and Water Consumption

“…The blood-brain barrier of Drosophila expresses multiple aquaporins and may potentially regulate hemolymph osmolality (Limmer et al, 2014). Whether changes in hemolymph osmolality are regulated by the blood-brain barrier to impact ISN activity is an interesting question for future study.…”

The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D

“…Expression of murine Bsg rescues the phenotypes associated with the loss bsg in the fly visual system, suggesting that they play similar functions in vivo (Curtin et al, 2005). An alternative model of lactate transport suggests that gap junctions may allow the direct cell-to-cell passage of lactate or glucose (Bosone et al, 2016; Hertz et al, 2007; Limmer et al, 2014; Tabernero et al, 2006). As Drosophila innexins are the equivalent of mammalian connexin proteins and form heteromeric and heterotypic gap junctions (Stebbings et al, 2002) , we also tested shaking B (s hakB ), a member of the innexin family (Phelan et al, 1998; Shimohigashi and Meinertzhagen, 1998).…”

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

“…Choosing the well-characterized Drosophila pSJ as the 'gold standard', we can consider structural and molecular equivalents along the branch points of metazoan evolution. The list of proteins associated with fly pSJ continues to grow and we will focus on the best-characterized members of that list (Limmer et al, 2014). At the core of the junction is a set of Drosophila proteins shown to be immobile in photobleaching studies; it includes the neurexin superfamily member neurexin IV (Nrx-IV), the L1 IgCAM family member neuroglian (Nrg), coracle (Cora), the Drosophila band 4.1 protein, and the ATPα and nervana 2 (Nrv2), subunits of the ion pump Na + / K + ATPase (Baumgartner et al, 1996;Genova and Fehon, 2003;Lamb et al, 1998;Laval et al, 2008;Oshima and Fehon, 2011).…”