Abstract
SummaryThe blood-brain barrier (BBB) is an essential system that isolates the central nervous system from the internal environment. Increasing evidence has begun to reveal the molecules that are required for BBB integrity. However, how these components are regulated remains unclear. Here we report that a matrix metalloproteinase, Mmp2, is essential for the establishment of the BBB in Drosophila. In the absence of mmp2, the BBB becomes leaky, which allows the tracer to penetrate the brain. Moreover, the expression pattern of a junctional component, Neuroglian, is altered. We also find that the regulation of the amounts of particular extracellular matrix components is critical for BBB establishment. Furthermore, the process of mesenchymal-epithelial transition of BBB-forming cells is perturbed in the absence of Mmp2. These data indicate that the presence of Mmp(s), which is typically considered to be a risk factor for BBB degradation, is essential for BBB integrity in Drosophila.
Highlights
The blood-brain barrier (BBB) is a tissue architecture that regulates the strongly ‘‘isolated’’ microenvironment of the central nervous system (CNS)
BBB-Specific Knockdown of Mmp2 Results in the Disruption of BBB Integrity To identify genes that are required for the integrity of BBB in Drosophila, we have conducted an in vivo RNA interference (RNAi)-based screen
When fluorescently labeled dextran (10 kDa) was injected as a tracer to monitor the integrity of BBB into the abdomen of adult animals that have intact BBB, it should be excluded from the CNS (Figure 1D) (Bainton et al, 2005)
Summary
The blood-brain barrier (BBB) is a tissue architecture that regulates the strongly ‘‘isolated’’ microenvironment of the central nervous system (CNS). In the mammalian CNS, the BBB is established by microvascular capillary endothelial cells. There are remarkable differences in the properties of vessels (capillaries) in the brain and periphery in vertebrates. In contrast to leaky vessels in peripheral organs (Mann et al, 1985), the BBB restricts the entry of polar molecules as well as peptides and proteins into the brain (Zlokovic et al, 1985; Zlokovic et al, 1985; Zlokovic and Apuzzo, 1997). Several BBB peptide transport mechanisms exist, for example, receptor-mediated, adsorptive-mediated, and carrier-mediated ones, as well as nonspecific passive diffusion (Zlokovic, 1995)
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