GPCR Signaling Is Required for Blood-Brain Barrier Formation in Drosophila

Schwabe, Tina; Bainton, Roland J.; Fetter, Richard D.; Heberlein, Ulrike; Gaul, Ulrike

doi:10.1016/j.cell.2005.08.037

Cited by 232 publications

(361 citation statements)

References 49 publications

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“…Invertebrate axons are insulated from their salt-rich environment through a glial-dependent BBB, which plays a crucial role in electrical and chemical insulation (Auld et al, 1995;Baumgartner et al, 1996;Bainton et al, 2005;Schwabe et al, 2005). Ultrastructural studies have demonstrated SJs between perineurial glial cells and inner glial cell membrane to form the structural basis of BBB of some insects (Carlson et al, 2000).…”

Section: Sjs As Molecular Barriers: a Common Theme In Axonal Insulationmentioning

confidence: 99%

“…Recent analyses of SJs in Drosophila show the presence of a number of proteins that are enriched at or associated with SJs (for review, see Banerjee et al, 2006). Interestingly, most of these proteins are localized at the epithelial SJs, only Neurexin IV (Nrx IV) and Gliotactin are reported to be functional in the peripheral glia, whereas Moody and Loco are required in the surface glia to achieve effective insulation of the CNS Schwabe et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System ofDrosophila

Banerjee¹,

Pillai²,

Paik³

et al. 2006

J. Neurosci.

104

171

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Axonal insulation is critical for efficient action potential propagation and normal functioning of the nervous system. In Drosophila, the underlying basis of nerve ensheathment is the axonal insulation by glial cells and the establishment of septate junctions (SJs) between glial cell membranes. However, the details of the cellular and molecular mechanisms underlying axonal insulation and SJ formation are still obscure. Here, we report the characterization of axonal insulation in the Drosophila peripheral nervous system (PNS). Targeted expression of tau-green fluorescent protein in the glial cells and ultrastructural analysis of the peripheral nerves allowed us to visualize the glial ensheathment of axons. We show that individual or a group of axons are ensheathed by inner glial processes, which in turn are ensheathed by the outer perineurial glial cells. SJs are formed between the inner and outer glial membranes. We also show that Neurexin IV, Contactin, and Neuroglian are coexpressed in the peripheral glial membranes and that these proteins exist as a complex in the Drosophila nervous system. Mutations in neurexin IV, contactin, and neuroglian result in the disruption of blood-nerve barrier function in the PNS, and ultrastructural analyses of the mutant embryonic peripheral nerves show loss of glial SJs. Interestingly, the murine homologs of Neurexin IV, Contactin, and Neuroglian are expressed at the paranodal SJs and play a key role in axon-glial interactions of myelinated axons. Together, our data suggest that the molecular machinery underlying axonal insulation and axon-glial interactions may be conserved across species.

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Section: Sjs As Molecular Barriers: a Common Theme In Axonal Insulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System ofDrosophila

Banerjee¹,

Pillai²,

Paik³

et al. 2006

J. Neurosci.

104

171

View full text Add to dashboard Cite

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“…Surface glia ensheath the brain and play a role in the formation of the blood-brain barrier. Cortex glia surround neurons and neuroblasts, while neuropile glia compartmentalize the neuropile, forming axon tracts for neurites (Chotard et al 2005;Pereanu et al 2005;Schwabe et al 2005). In addition, another subset of glia, the retinal basal glia, are born in the optic stalk and migrate into the eye imaginal disc (Choi and Benzer 1994;Rangarajan et al 1999).…”

mentioning

confidence: 99%

“…Disruption of loco gene function leads to multiple defects during development in Drosophila (Granderath et al 1999;Pathirana et al 2001;Yu et al 2005). In loco loss-of-function mutant embryos, failure of glial differentiation leads to improper ensheathing of neuronal axons and, consequently, the blood-brain barrier is disrupted (Granderath et al 1999;Schwabe et al 2005). Biochemical studies in Drosophila embryos have shown that Loco regulates these processes by direct physical interaction with G-protein subunits (Schwabe et al 2005).…”

mentioning

confidence: 99%

“…In loco loss-of-function mutant embryos, failure of glial differentiation leads to improper ensheathing of neuronal axons and, consequently, the blood-brain barrier is disrupted (Granderath et al 1999;Schwabe et al 2005). Biochemical studies in Drosophila embryos have shown that Loco regulates these processes by direct physical interaction with G-protein subunits (Schwabe et al 2005). While the molecular and genetic mechanisms that control asymmetric division of Drosophila embryonic neuroblasts have been studied extensively Jan 1998, 2001;Chia and Yang 2002;Pearson and Doe 2003;Betschinger and Knoblich 2004), the genetic components that regulate asymmetric division of neuroblasts in the postembryonic nervous system are less well understood.…”

mentioning

confidence: 99%

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Regulation of Glia Number in Drosophila by Rap/Fzr, an Activator of the Anaphase-Promoting Complex, and Loco, an RGS Protein

2008

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Glia mediate a vast array of cellular processes and are critical for nervous system development and function. Despite their immense importance in neurobiology, glia remain understudied and the molecular mechanisms that direct their differentiation are poorly understood. Rap/Fzr is the Drosophila homolog of the mammalian Cdh1, a regulatory subunit of the anaphase-promoting complex/cyclosome (APC/C). APC/C is an E3 ubiquitin ligase complex well characterized for its role in cell cycle progression. In this study, we have uncovered a novel cellular role for Rap/Fzr. Loss of rap/fzr function leads to a marked increase in the number of glia in the nervous system of third instar larvae. Conversely, ectopic expression of UAS-rap/fzr, driven by repo-GAL4, results in the drastic reduction of glia. Data from clonal analyses using the MARCM technique show that Rap/Fzr regulates the differentiation of surface glia in the developing larval nervous system. Our genetic and biochemical data further indicate that Rap/Fzr regulates glial differentiation through its interaction with Loco, a regulator of G-protein signaling (RGS) protein and a known effector of glia specification. We propose that Rap/Fzr targets Loco for ubiquitination, thereby regulating glial differentiation in the developing nervous system.

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Neonatal Rat Primary Microglia: Isolation, Culturing, and Selected Applications

Aschner

2010

CP Toxicology

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Microglial cells elaborate trophic factors and cytokines and remove toxins and debris from the extracellular space, acting analogously to peripheral macrophages. Over the past two decades increased attention has been directed at the role of microglia, not only in normal physiology, but also in mediating neurotoxicity. Activation of microglia is inherent to multiple neurodegenerative disorders and exposure to toxic compounds. In large measure, these revelations have come about as a result of technologies that enable researchers to obtain high-yield and -purity primary cultures of rodent microglia. The mechanical isolation protocol discussed in this protocol offers an economical method to isolate large amount of microglia in a short and not too labor intensive manner. Most importantly, it assures a high yield of cells with great reproducibility. Given the ever increasing importance of microglia to the field of neurotoxicology research, the ability to isolate high yield of primary microglia makes it possible to investigate the role and mechanisms associated with microglial modulation of neurotoxicity. We provide a detailed description on the methods that is routinely used in our laboratory for the isolation and culturing of microglia, with emphasis on the steps which are deemed most critical for obtaining pure and healthy cultures.

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GPCR Signaling Is Required for Blood-Brain Barrier Formation in Drosophila

Cited by 232 publications

References 49 publications

Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System ofDrosophila

Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System ofDrosophila

Regulation of Glia Number in Drosophila by Rap/Fzr, an Activator of the Anaphase-Promoting Complex, and Loco, an RGS Protein

Neonatal Rat Primary Microglia: Isolation, Culturing, and Selected Applications

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