Researchers Detect a Diffusion Barrier Inside Fly Brain

Summary: In fruit flies, there is a second barrier in the brain where glial cells ensure a spatial separation for different functional compartments.

Source: University of Munster

The neurons, located in the brain are interconnected in a complex pattern and establish special communication points, the synapses. All neurons require a constant environment in order to function reliably. To ensure this, the brain is surrounded by the so-called blood-brain barrier. It ensures, for example, that the nutrient balance always remains the same and that harmful influences do not reach the neurons. This applies to all animals including humans.

For insects, a team led by Nicole Pogodalla and Prof. Dr. Christian Klämbt from the Institute of Neuro- and Behavioral Biology at the University of Münster (Germany) has now shown that there is also a second barrier in the brain. Here glial cells, too, ensure a spatial separation of different functional compartments, which is essential for reliable functioning of the nervous system.

The work was published in the prestigious online journal Nature Communications.

The research team studied the insect brain using larvae of the fruit fly (Drosophila melanogaster) as an example and focused on the role of glial cells. Early in development these cells help to establish the correct neuronal network and later glial cells play important roles in controlling the transmission of signals between neurons. In all invertebrates, as well as in primitive vertebrates, glial cells also define the outer boundary of the nervous system—the blood-brain barrier.

This shows a cross section of a fly brain
Optical cross-section through a fly brain. The green coloring indicates the distribution of the extracellular matrix protein “Trol”, which is formed by all enveloping glial cells. The subdivision of the brain into different reaction spaces becomes clear. Credit: WWU – Nicole Pogodalla und Christian Klämbt

Deep in the fly brain, all synapses are located in a special region called the neuropil. The neuropil is separated from the zone containing the cell bodies of the neurons by a small set of surrounding glial cells, that were in the focus of Nicole Pogodalla. She developed a new experimental approach—dye injections into living larval brains—and combined this with cell type specific ablation experiments to show that these glial cells actually form a diffusion barrier, i.e. regulate the distribution of molecules.

Since all other cellular barriers in the body are formed by polarized cells that have an “up” and a “down,” the research team next examined glial cell polarity. Using advanced confocal image analysis as well as electron microscopy work in combination with state-of-the-art molecular genetics, the researchers uncovered that the ensheathing glial cells are indeed polarized.

They showed that this polarization is functionally important, as defects in polarity lead to both an altered cell shape and cause a significant behavioral phenotype in fly larvae: Movement of larvae with defective or absent glial cells is impaired, and crawling speed is reduced.

In the current paper, the research team also describes the importance of extracellular matrix—the tissue lying between cells -, membrane lipids and membrane proteins, as well as the function of the cytoskeleton in the formation of the barrier-forming glial cells.

About this neuroscience research news

Author: Press Office
Source: University of Munster
Contact: Press Office – University of Munster
Image: The image is credited to WWU – Nicole Pogodalla and Christian Klämbt

Original Research: Open access.
Drosophila ßHeavy-Spectrin is required in polarized ensheathing glia that form a diffusion-barrier around the neuropil” by Nicole Pogodalla et al. Nature Communications


Drosophila ßHeavy-Spectrin is required in polarized ensheathing glia that form a diffusion-barrier around the neuropil

In the central nervous system (CNS), functional tasks are often allocated to distinct compartments. This is also evident in the Drosophila CNS where synapses and dendrites are clustered in distinct neuropil regions. The neuropil is separated from neuronal cell bodies by ensheathing glia, which as we show using dye injection experiments, contribute to the formation of an internal diffusion barrier.

We find that ensheathing glia are polarized with a basolateral plasma membrane rich in phosphatidylinositol-(3,4,5)-triphosphate (PIP3) and the Na+/K+-ATPase Nervana2 (Nrv2) that abuts an extracellular matrix formed at neuropil-cortex interface.

The apical plasma membrane is facing the neuropil and is rich in phosphatidylinositol-(4,5)-bisphosphate (PIP2) that is supported by a sub-membranous ßHeavy-Spectrin cytoskeleton. ßHeavy-spectrin mutant larvae affect ensheathing glial cell polarity with delocalized PIP2 and Nrv2 and exhibit an abnormal locomotion which is similarly shown by ensheathing glia ablated larvae. Thus, polarized glia compartmentalizes the brain and is essential for proper nervous system function.

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