Organization and Function of the Blood–Brain Barrier inDrosophila

Abstract

The function of a complex nervous system depends on an intricate interplay between neuronal and glial cell types. One of the many functions of glial cells is to provide an efficient insulation of the nervous system and thereby allowing a fine tuned homeostasis of ions and other small molecules. Here, we present a detailed cellular analysis of the glial cell complement constituting the blood-brain barrier in Drosophila. Using electron microscopic analysis and single cell-labeling experiments, we characterize different glial cell layers at the surface of the nervous system, the perineurial glial layer, the subperineurial glial layer, the wrapping glial cell layer, and a thick layer of extracellular matrix, the neural lamella. To test the functional roles of these sheaths we performed a series of dye penetration experiments in the nervous systems of wild-type and mutant embryos. Comparing the kinetics of uptake of different sized fluorescently labeled dyes in different mutants allowed to conclude that most of the barrier function is mediated by the septate junctions formed by the subperineurial cells, whereas the perineurial glial cell layer and the neural lamella contribute to barrier selectivity against much larger particles (i.e., the size of proteins). We further compare the requirements of different septate junction components for the integrity of the blood-brain barrier and provide evidence that two of the six Claudin-like proteins found in Drosophila are needed for normal bloodbrain barrier function.

Multiple pathways mediate the sex-peptide-regulated switch in female Drosophila reproductive behaviours

“…In SPR mutant females, SP present in the haemolymph (see the electronic supplementary material, figure S1) seems not to reach neuronal target(s), which are separated from the haemolymph by a sheath of glial cells forming the BBB [32,33]. We therefore wanted to know whether a leaky BBB would allow SP to reach its neuronal target(s) and restore the SP response in SPR mutant females in the physiological context of mating.…”

Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension

“…Such a relationship between recruited immune cells and neural growth has been suggested for murine models of NF1 (38). Another possibility is that plasmatocytes are recruited as part of the natural process of neural growth, because they are important for deposition of the outermost basal laminalike structure (neural lamella) on growing nerves (39). However, the lack of plasmatocytes on the enlarged nerves in larvae with constitutively active RAS argues against this interpretation, and additional studies are required to establish the link between recruited plasmatocytes and the neural growth in egh mutants.…”

Lipoprotein Particles Cross the Blood–Brain Barrier inDrosophila

“…Their lipoproteins and lipoprotein receptors resemble those of vertebrates (van der Horst et al, 2002;Van der Horst et al, 2009;Khaliullina et al, 2010) and the functionally conserved BBB is formed by septate junctions composed of molecules almost identical to those in vertebrate tight junctions (Awasaki et al, 2008;Stork et al, 2008;Mayer et al, 2009). Here, we investigate whether the Drosophila lipoprotein lipophorin (Lpp) crosses the larval BBB, and whether it influences larval brain development.…”